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Insulin Response (insulin + response)

Distribution by Scientific Domains

Medical Sciences	65%
Life Sciences	34%

Distribution within Medical Sciences

Diabetes	21%
Pharmacology & Pharmaceutical Medicine	16%
General & Internal Medicine	12%

Selected Abstracts

Greater growth hormone and insulin response in women than in men during repeated bouts of sprint exercise

ACTA PHYSIOLOGICA, Issue 2 2009
M. Esbjörnsson
Abstract Aim:, In a previous study, sprint training has been shown to increase muscle cross-sectional area in women but not in men [Eur J Appl Physiol Occup Physiol 74 (1996) 375]. We hypothesized that sprint exercise induces a different hormonal response in women than in men. Such a difference may contribute to explaining the observed gender difference in training response. Method:, Metabolic and hormonal response to three 30-s sprints with 20-min rest between the sprints was studied in 18 physically active men and women. Results:, Accumulation of blood lactate [interaction term gender (g) × time (t): P = 0.022], and plasma ammonia (g × t: P < 0.001) after sprint exercise was greater in men. Serum insulin increased after sprint exercise more so in women than in men (g × t: P = 0.020), while plasma glucose increased in men, but not in women (g × t: P < 0.001). Serum growth hormone (GH) increased in both women and men reaching similar peak levels, but with different time courses. In women the peak serum GH level was observed after sprint 1, whereas in men the peak was observed after sprint 3 (g × t; P < 0.001). Serum testosterone tended to decrease in men and increase in women (g × t: P = 0.065). Serum cortisol increased approx. 10,15% after sprint exercise, independent of gender (time: P = 0.005). Conclusion:, Women elicited a greater response of serum GH and insulin to sprint exercise. This may contribute to explaining the earlier observed muscle hypertrophy in women in response to sprint training. [source]

Balancing needs and means: the dilemma of the ,-cell in the modern world

DIABETES OBESITY & METABOLISM, Issue 2009
G. Leibowitz
The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of ,-cell function coexists. This is demonstrated by the fact that near-physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin-deficient type 1 diabetics. The normal ,-cell adapts well to the demands of insulin resistance. Also in hyperglycaemic states some degree of adaptation does exist and helps limit the severity of disease. We demonstrate here that the mammalian target of rapamycin (mTOR) system might play an important role in this adaptation, because blocking mTORC1 (complex 1) by rapamycin in the nutritional diabetes model Psammomys obesus caused severe impairment of ,-cell function, increased ,-cell apoptosis and progression of diabetes. On the other hand, under exposure to high glucose and FFA (gluco-lipotoxicity), blocking mTORC1 in vitro reduced endoplasmic reticulum (ER) stress and ,-cell death. Thus, according to the conditions of stress, mTOR may have beneficial or deleterious effects on the ,-cell. ,-Cell function in man can be reduced without T2DM/impaired glucose tolerance (IGT). Prospective studies have shown subjects with reduced insulin response to present, several decades later, an increased incidence of IGT/T2DM. From these and other studies we conclude that T2DM develops on the grounds of ,-cells whose adaptation capacity to increased nutrient intake and/or insulin resistance is in the lower end of the normal variation. Inborn and acquired factors that limit ,-cell function are diabetogenic only in a nutritional/metabolic environment that requires high functional capabilities from the ,-cell. [source]

Minor long-term changes in weight have beneficial effects on insulin sensitivity and ,-cell function in obese subjects

DIABETES OBESITY & METABOLISM, Issue 1 2002
A. M. Rosenfalck
SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG) and ,-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2. Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p =,0.038) and 2 h (p =,0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = , 0.83, p =,0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p =,0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance. [source]

Diabetes mellitus and alcohol

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004
Albert van de Wiel
Abstract Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes

DRUG DEVELOPMENT RESEARCH, Issue 8 2006
David M. Webb
Abstract The risks of cardiovascular disease (CVD) and type 2 diabetes increase as body mass index increases in overweight (25,30,kg/m2) and obese (>30,kg/m2) individuals. However, these risks can be reduced with even modest weight loss. In patients with established type 2 diabetes, control of both glycemia and body weight are important to minimize the risk of future diabetic complications. Exenatide is a 39-amino-acid peptide incretin mimetic currently approved in the United States for the treatment of type 2 diabetes as an adjunct to sulfonylurea and/or metformin. Phase-3 clinical studies showed exenatide therapy for 30 weeks significantly reduced glycosylated hemoglobin (HbA1c), and fasting and postprandial plasma glucose, while significantly reducing body weight. Open-label extensions from these pivotal trials demonstrated patients treated with exenatide for 2 years had sustained reductions in glycemic control at 30 weeks and a progressive reduction in body weight. Patients treated with exenatide also had improvement in blood pressure, inflammatory markers, and lipid profiles. The glucoregulatory and weight-reducing effects of exenatide are the result of multiple modes of action that mimic several of the glucoregulatory actions of the naturally occurring peptide, glucagon-like peptide-1 (GLP-1). These include restoration of first phase insulin response, enhancement of glucose-dependent insulin secretion, suppression of inappropriate glucagon secretion, slowing of gastric emptying, and affects on satiety leading to reduced food intake. Further research is required to fully understand the role for exenatide to potentially alleviate metabolic disorders associated with type 2 diabetes, including CVD and obesity. Drug Dev. Res. 67:666,676, 2006. © 2006 Wiley-Liss, Inc. [source]

Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005
A. Kriketos
Abstract Background, Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. Materials and methods, Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. Results, The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44·6 ± 4·9 vs. 60·0 ± 4·8 µmol min,1 kg FFM,1, P = 0·037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180,240 min (,0·77 ± 0·11 mmol L,1), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2·13 ± 0·51 vs. 0·70 ± 0·35 mmol L,1, P = 0·03), only in the REL. Conclusions, These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver. [source]

Liraglutide: can it make a difference in the treatment of type 2 diabetes?

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2010
J. Unger
Summary Despite advances in the management of type 2 diabetes, glycaemic control remains suboptimal for many patients because of the complexities of disease progression and the need to balance improved glycaemic control against adverse treatment effects, particularly weight gain and hypoglycaemia. Thus, the development of new antidiabetes therapies continues in earnest. Incretin hormones have been the recent focus of research, as they account for up to 70% of the insulin response following a meal. There is also a high concordance between the physiological actions of one hormone, glucagon-like peptide-1 (GLP-1), and the therapeutic needs of patients. As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). Liraglutide, a human GLP-1 analogue sharing 97% of its amino acid sequence identity with native GLP-1, has been approved for use as monotherapy (not in Europe) and in combination with selected oral agents. In this supplement, we summarise key liraglutide data, offer practical insight into what we might expect of liraglutide in clinical use and examine selected case studies. For reasons of the safety and efficacy of GLP-1 receptor agonists, many thought leaders believe that these will become background therapy for majority of patients in the coming years. This supplement will serve as a resource from which readers can extract information concerning the potential benefits for patients who are overweight, losing pancreatic beta-cell function and drifting towards the ravaging effects of chronic hyperglycaemia. [source]

Effects of oat processing on the glycaemic and insulin responses in horses

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2003
I. Vervuert
Summary This study was conducted to evaluate the effects of different oat processing techniques on the plasma glucose and insulin response in horses. In a cross-over design, six horses (ages 4,15 years, mean body weight ± SD: 450 ± 37 kg) were fed in random order: untreated oats, finely ground, steam-flaked and popped oats. The total oat intake varied between 1.05,1.5 kg/day, and the amount of diet was adjusted to a starch content of 630 g starch per day and horse (1.2,1.5 g starch/kg BW/day). During the stabilization period of 10 days, horses additionally received 6 kg grass hay. Following this adaptation period, plasma glucose and insulin responses to the respective dietary treatments were tested. Horses were fed their test diet (exclusively oats), and blood samples were collected at defined times to determine glycaemic and insulin response. Oat feeding resulted in a significant increase in mean plasma glucose and insulin concentration. However, glucose and insulin peaks as well as their respective areas under the curves were not clearly influenced by oat processing. The glycaemic index varied between 94.7 ± 11.2% (steam-flaked oats) and 102.6 ± 14.5% (finely ground oats, n.s.), the insulin index ranged between 93.8 ± 18.9% (popped oats) and 150.0 ± 77.6% (finely ground oats, n.s.). The insulin reaction to oat feeding showed a high variability between the horses. The results of this study indicate that the glucose and insulin responses are not clearly altered by the different types of oat processing. However, the glucose and insulin responses tended to be lower in thermally treated oats when compared with untreated or finely ground oats. [source]

Essential role of PSM/SH2-B variants in insulin receptor catalytic activation and the resulting cellular responses

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2008
Manchao Zhang
Abstract The positive regulatory role of PSM/SH2-B downstream of various mitogenic receptor tyrosine kinases or gene disruption experiments in mice support a role of PSM in the regulation of insulin action. Here, four alternative PSM splice variants and individual functional domains were compared for their role in the regulation of specific metabolic insulin responses. We found that individual PSM variants in 3T3-L1 adipocytes potentiated insulin-mediated glucose and amino acid transport, glycogenesis, lipogenesis, and key components in the metabolic insulin response including p70 S6 kinase, glycogen synthase, glycogen synthase kinase 3 (GSK3), Akt, Cbl, and IRS-1. Highest activity was consistently observed for PSM alpha, followed by beta, delta, and gamma with decreasing activity. In contrast, dominant-negative peptide mimetics of the PSM Pro-rich, pleckstrin homology (PH), or src homology 2 (SH2) domains inhibited any tested insulin response. Potentiation of the insulin response originated at the insulin receptor (IR) kinase level by PSM variant-specific regulation of the Km (ATP) whereas the Vmax remained unaffected. IR catalytic activation was inhibited by peptide mimetics of the PSM SH2 or dimerization domain (DD). Either peptide should disrupt the complex of a PSM dimer linked to IR via SH2 domains as proposed for PSM activation of tyrosine kinase JAK2. Either peptide abolished downstream insulin responses indistinguishable from PSM siRNA knockdown. Our results implicate an essential role of the PSM variants in the activation of the IR kinase and the resulting metabolic insulin response. PSM variants act as internal IR ligands that in addition to potentiating the insulin response stimulate IR catalytic activation even in the absence of insulin. J. Cell. Biochem. 103: 162,181, 2008. © 2007 Wiley-Liss, Inc. [source]

Updating the effects of fatty acids on skeletal muscle

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008
Leonardo R. Silveira
In this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long-chain acyl-coenzyme A (LCA-CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate-1/2 (IRS), phosphatidylinositol-3-kinase, (PI3-kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor-kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNF,), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle. J. Cell. Physiol. 217: 1,12, 2008. © 2008 Wiley-Liss, Inc. [source]

Cigarette smoking, oral moist snuff use and glucose intolerance

JOURNAL OF INTERNAL MEDICINE, Issue 2 2000
P.-G. Persson
Abstract. Persson P-G, Carlsson S, Svanström L, Östenson C-G, Efendic S, Grill V (Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden). Cigarette smoking, oral moist snuff use and glucose intolerance. J Intern Med 2000; 248: 103,110. Objective. To investigate the association between cigarette smoking and use of oral moist snuff and impaired glucose tolerance and type 2 diabetes. Design. We performed a population-based cross-sectional study of glucose intolerance and tobacco use in Stockholm during 1992,94. The sample consisted of 3128 men, aged 35,56 years, of whom 52% had a family history of diabetes. In an oral glucose tolerance test, we detected 55 men with type 2 diabetes and 172 with impaired glucose tolerance. Information on cigarette smoking and oral moist snuff use was collected by a questionnaire. Results. The odds ratio of type 2 diabetes was increased for smokers of 25+ cigarettes day,1 (odds ratio = 2.6, 95% confidence interval = 1.1,5.9) as well as for moist snuff dippers of 3+ boxes week,1 (odds ratio = 2.7, 95% confidence interval = 1.3,5.5). The odds ratio of relatively high (highest tertile) fasting insulin levels in subjects with impaired glucose tolerance associated with cigarette smoking of 25+ cigarettes day,1 was 1.5 (95% confidence interval = 0.7,3.6). The corresponding estimate of a relatively low (lowest tertile) 2 h insulin response was 2.5 (95% confidence interval = 0.9,7.1). Conclusions. These results indicate that heavy users of cigarettes or moist snuff have an increased risk of type 2 diabetes. The results could suggest that tobacco use is associated with a low insulin response. [source]

Age and gender differences in body composition, energy expenditure, and glucoregulation of adult rhesus monkeys

JOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2000
Jon J. Ramsey
The purpose of this study was to examine the relationship of age to body composition, glucoregulation, activity, and energy expenditure in male and female rhesus monkeys. The animals were studied in three groups, young adults (YA, 7,9 years), middle-aged adults (MA, 13,17 years), and older adults (OA,>23 years) adults. OA had a lower ( P<0.05) lean body mass than the YA and MA. OA also had the lowest values (P<0.06) for energy expenditure (kJ/minute). Age-related differences (P<0.05) were observed in time spent resting and moving. The OA spent the most time resting and the least time in vertical movement. There was a trend towards an age-related decrease in acute insulin response to glucose, while other glucoregulatory parameters were not changed with age. These results are similar to findings in humans, providing further evidence that the rhesus monkey is an appropriate model of human aging. [source]

The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2009
T. Edholm
Abstract, Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L,1) or GLP-1 (10 nmol L,1) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1,400 pmol kg,1 min,1) or GLP-1 (0.1,20 pmol kg,1 min,1). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6,16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2. [source]

Limitations of first-phase insulin response to evaluate insulin secretion in children

PEDIATRIC DIABETES, Issue 1 2000
WS Cutfield
The first-phase insulin response (FPIR) is a widely used method to evaluate beta-cell function during the prediabetic phase of evolving type 1 diabetes mellitus (DM). The aim of the present study was to evaluate the influence of clinical and methodological variables on FPIR in normal children and adolescents. Children and adolescents who were first-degree relatives of those with type 1 DM and healthy young adults were studied. All subjects were islet cell antibody-negative. A FPIR test was performed on all subjects while fasting. Insulin samples were drawn at 0, 1, 2, 3, 4, 5, 6, 8, and 10 min after 0.3 g/kg of dextrose. FPIR(1,10) was calculated as the area under the FPIR curve corrected for baseline. Eighty-five subjects aged 4,22 yr were studied, 43 of whom were pre-pubertal, 24 pubertal, and 18 post-pubertal. FPIR(1,10) values were lower in the pre-pubertal group when compared to either the pubertal and post-pubertal groups (415 [179,965, 2SD], 756 [256,2,223] and 684 [235,1,180] mU/L, respectively; p<0.05). Obese subjects had a higher FPIR than non-obese subjects (856 vs. 520 mU/L; p<0.005). Despite correcting for the influence of puberty and obesity, there remained considerable unaccounted variability in FPIR(1,10) (R=0.46). Further variables found to influence FPIR(1,10) were: fasting insulin level (r2=0.49); weight for length index (r2=0.38); peak blood glucose level (r2=0.38, all p<0.001); and pre-pubertal age (r2=0.20, p<0.05). Conclusion: FPIR exhibited wide inter-subject variability and was influenced by a number of clinical and methodological factors that make interpretation more difficult without more specifically defined standards. [source]

Effects of twin pregnancy and periconceptional undernutrition on maternal metabolism, fetal growth and glucose,insulin axis function in ovine pregnancy

THE JOURNAL OF PHYSIOLOGY, Issue 5 2008
C. W. H. Rumball
Although twins have lower birthweights than singletons, they may not experience the increased disease risk in adulthood reportedly associated with low birthweight. In contrast, another periconceptional event, maternal undernutrition, does not reduce birthweight but does affect fetal and postnatal physiology in sheep. We therefore studied maternal and fetal metabolism, growth and glucose,insulin axis function in late gestation in twin and singleton sheep pregnancies, either undernourished from 60 days before until 30 days after conception or fed ad libitum. We found that twin-bearing ewes had decreased maternal food intake in late gestation and lower maternal and fetal plasma glucose and insulin levels. Twin fetuses had fewer everted placentomes, grew slower in late gestation, and had a greater insulin response to a glucose challenge, but lesser response to arginine. In contrast, periconceptional undernutrition led to increased maternal food intake and a more rapid fall in maternal glucose levels in response to fasting. Periconceptional undernutrition increased the number of everted placentomes, and abolished the difference in insulin responses to glucose between twins and singletons. Thus, the physiology of twin pregnancy is quite different from that of singleton pregnancy, and is probably determined by a combination of factors acting in both early and late gestation. The inconsistency of the relationships between low birthweight and postnatal disease risk of twins may lie in their very different fetal development. These data suggest that twin pregnancy may be another paradigm of developmental programming, and indicate that twins and singletons must be examined separately in any study of fetal or postnatal physiology. [source]

Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency

ANNALS OF NEUROLOGY, Issue 1 2010
Cigdem I. Akman MD
Objective Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Methods Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT. Results The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance. Interpretation This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism. ANN NEUROL 2010;67:31,40 [source]

Food factors and gastrointestinal function: A critical interface

BIOFACTORS, Issue 1-4 2004
Barbara Schneeman
Abstract The gastrointestinal tract (GIT) is an interface between the external environment and the body and functions to extract nutrients from foods as well as handle the various non-nutrient compounds found in foods. Thus factors in foods that affect health and disease may mediate their effects either through a direct effect on the GIT or indirectly by the pattern of absorption and subsequent metabolism through the GIT. To explore this relationship one must consider both the physiological responses of the GIT induced by factors in foods as well as the implications of GIT adaptation for metabolism. Metabolic adaptations to dietary factors such as cholesterol levels, glucose and insulin response, and immune function appear to be modulated by the manner in which food factors are metabolized in the GIT. New research is needed to understand the inter-relationship between food factors that stimulate GIT response and the subsequent influence on metabolism that influences risk factors for disease and health promotion. [source]

Noncompartmental pharmacokinetics analysis of glucose-stimulated insulin response in African,American and Caucasian youths

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2009
Lanyi Xie
Abstract The objective of this study was to examine the differences in glucose and insulin responses between African,American and Caucasian youths and to determine the associations of between-group differences with sex, body mass index (BMI) and pubertal status using a noncompartmental pharmacokinetic approach. Sixteen African,American and 22 Caucasian healthy adolescents were tested using the frequently sampled intravenous glucose tolerance test. Longitudinal t -tests across each observation revealed that (1) African,American youths have higher insulin concentrations between 4 to 19,min; (2) insulin levels remained similar as subjects were grouped according to sex and pubertal status; (3) for glucose, the only difference was found as it approached steady-state basal level (>100,min) between groups with different BMIs. Linear regression showed that insulin concentrations between 4 to 19,min are associated with BMI in Caucasians. African,American youths were found to have higher insulin responses after glucose stimulation and the insulin concentrations were more related to BMI in Caucasians compared with African,Americans. BMI also has a significant effect on the glucose steady state basal level. The acute insulin response to glucose (AIRg) extended to 20,min resulted in a more significant racial difference (p<0.0006) compared with the calculation done over 10,min suggested in the past (p<0.001). Copyright © 2009 John Wiley & Sons, Ltd. [source]

Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2009
Patricia N. Sidharta
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Urotensin-II (U-II) is one of the most potent vasoconstrictors identified thus far. , Although differences in both U-II blood levels and U-II receptor (UT-receptor) expression have been observed in patients with cardiovascular and cardiorenal disease, the precise function in humans has not been elucidated. , U-II and its receptor have been reported to be involved in glucose metabolism and insulin resistance, which can lead to the development of Type 2 diabetes mellitus. , In rat models of diabetes, palosuran, a selective, potent antagonist of the human UT-receptor, improved several disease markers. WHAT THIS STUDY ADDS , In this study in diabetic patients, the effects of palosuran on insulin secretion and sensitivity were investigated using a hyperglycaemic glucose clamp and a meal tolerance test and daily glucose levels were also studied. , Although no obvious beneficial effect of palosuran in this patient population was observed, the study contributes to providing more insight inro the human U-II/UT-receptor system. AIMS To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study. METHODS After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d., effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake. RESULTS Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of ,1.8 µU ml,1, 95% confidence interval (CI) ,7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean Cmax and AUC, (95% CI) and median tmax (range) in this patient population were 180 ng ml,1 (125, 260), 581 ng·h ml,1 (422, 800) and 3.0 h (0.67, 4.3), respectively. CONCLUSIONS The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes. [source]

Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease?

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001
John P Newnham
SUMMARY 1. The intra-uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant ,programming' before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra-uterine triggers appear to programme the individual's metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure. 2. Over the past decade, a series of studies in sheep have focused on the perinatal and life-long consequences of glucocorticoid exposure in mid- to late-pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound-guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction. 3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow-up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age. 4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions. [source]

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

CLINICAL ENDOCRINOLOGY, Issue 1 2005
Yi-Jen Hung
Summary Objective, This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, ,-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). Methods, Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) , 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. Results, After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4·25 ± 0·22 vs 4·80 ± 0·17 mmol/l, P < 0·001), high-density lipoprotein cholesterol (HDL-C) (1·25 ± 0·07 vs 1·43 ± 0·06 mmol/l, P < 0·05), and low-density lipoprotein cholesterol (LDL-C) (2·70 ± 0·15 vs 3·37 ± 0·17 mmol/l, P < 0·05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic ,-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0·38 ± 0·06 vs 0·54 ± 0·09 × 10,5 min,1/pmol, P < 0·05; 0·017 ± 0·002 vs 0·021 ± 0·001 min,1, P < 0·05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0·05). Conclusion, Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on ,-cell secretory function. [source]

The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients

CLINICAL ENDOCRINOLOGY, Issue 1 2003
Anna Maria Di Blasio
Summary objective ,We have recently reported that, in healthy elderly Dutch individuals, a N363S polymorphism in the glucocorticoid receptor (GR) gene is associated with higher sensitivity to low-dose dexamethasone (0·25 mg), evaluated as both cortisol suppression and insulin response, and with an increased body mass index (BMI). In the present study we investigated the role of the N363S polymorphism, and a BclI restriction site polymorphism in a group of Italian patients with severe obesity. design Two hundred and seventy-nine patients (mean BMI 45·9 ± 0·9 kg/m2) were genotyped using both PCR-restriction fragment length polymorphism analysis and Taqman Sequence Detection System. Determination of several metabolic and antropometric parameters was also performed in order to correlate them to the genotype. results In this group of obese patients, 13 subjects (eight female, five males) were heterozygous for the N363S variant (allelic frequency 2·3%) and had significantly higher BMI (P < 0·04), resting energy expenditure (P < 0·03) and food intake (P < 0·01) when compared to wild-type homozygotes. When the data were analysed according to sex, female heterozygotes for the N363S allele had significantly higher BMI (P = 0·04), resting energy expenditure (P = 0·03) and food intake (P = 0·008) than obese women with the wild-type 363 GR gene. Male carriers of this variant also had higher values for these variables although the differences did not reach statistical significance. A case,control study with homozygous wild-type obese subjects which were age-, sex- and BMI-matched, revealed no difference in resting energy expenditure and food intake. The allele frequency of the BclI variant was 27% (89 females and 41 males out of 269 subjects). No differences in anthropometric and metabolic parameters were found between subjects heterozygous or homozygous for this variant GR in this obese population. However, when we studied the effect of the presence of the BclI polymorphism and the N363S variant in the same individual, we found that the subjects who carried both polymorphisms had a tendency towards higher systolic and diastolic blood pressure and significantly higher total and LDL-cholesterol levels (P = 0·005 and P = 0·05, respectively). discussion Taking the results of this study and those obtained in the Dutch population, we speculate that heterozygous carriers of the N363S variant who develop obesity, may become even more obese, possibly because they have a hypersensitive insulin response and thus, via activation of lipogenesis, store fat more efficiently. Furthermore, these data suggest that N363S carriers who carry the BclI polymorphism as well, tend to have a slightly unfavourable cardiovascular profile. [source]

Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2002
Jens Juul Holst
Abstract GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A1C, and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase-IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP-1-based therapy of type 2 diabetes, therefore, represents a new and attractive alternative. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Effects of oat processing on the glycaemic and insulin responses in horses

Essential role of PSM/SH2-B variants in insulin receptor catalytic activation and the resulting cellular responses

Role for the Pineal and Melatonin in Glucose Homeostasis: Pinealectomy Increases Night-Time Glucose Concentrations

JOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2001
S. E. La Fleur
Abstract The effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24-h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24-h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24-h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24-h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24-h rhythm. Melatonin treatment also resulted in higher meal-induced insulin responses, probably mediated via an increased sensitivity of the ,-cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic ,-cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only. [source]

Inflammatory change of fatty liver induced by intraportal low-dose lipopolysaccharide infusion deteriorates pancreatic insulin secretion in fructose-induced insulin-resistant rats

LIVER INTERNATIONAL, Issue 8 2008
Po-Shiuan Hsieh
Abstract Background: This study tested whether subacute inflammatory change of fatty liver induced by portal endotoxaemia is detrimental to pancreatic insulin secretion in fructose-fed rats (FFRs) with fatty liver. Methods: Rats were randomly assigned into two groups with a regular or fructose-enriched diet for 8 weeks. Rats, after fructose feeding for 4 weeks, were further divided into three subgroups: on fructose diet alone, on fructose diet combined with intraportal saline or lipopolysaccharide (LPS) infusion (n=8 per group) for the next 4 weeks. In another set of experiments, the liver and pancreatic tissues were obtained for histological examination in these four groups. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. Results: Fasting plasma insulin concentrations and homoeostasis model assessment-insulin resistance, an insulin resistance score, were significantly increased in FFRs but failed to change in rats with LPS treatment. The 4-week intraportal LPS infusion significantly increased circulating aspartate transaminase, alanine transaminase and C-reactive protein levels but did not alter endotoxin levels in FFRs. The increased white blood cell count was also noted in rats after intraportal LPS infusion for 2 and 4 weeks. The attenuated first-phase and second-phase insulin responses in FFRs shown in hyperglycaemic clamp were further deteriorated in those with intraportal LPS infusion. Increased histopathological scores of liver and pancreas shown in FFRs were further increased in those combined with portal endotoxaemia. Conclusion: This study demonstrates that the chronic subacute inflammatory change of fatty liver induced by mild portal endotoxaemia could deteriorate insulin secretion in a rodent model of metabolic syndrome and fatty liver. [source]

Effects of soy vs. casein protein on body weight and glycemic control in female monkeys and their offspring

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009
Janice D. Wagner
Abstract Nutritional interventions are important for reducing obesity and related conditions. Soy is a good source of protein and also contains isoflavones that may affect plasma lipids, body weight, and insulin action. Described here are data from a monkey breeding colony in which monkeys were initially fed a standard chow diet that is low fat with protein derived from soy. Monkeys were then randomized to a defined diet with a fat content similar to the typical American diet (TAD) containing either protein derived from soy (TAD soy) or casein,lactalbumin (TAD casein). The colony was followed for over two years to assess body weight, and carbohydrate and lipid measures in adult females (n=19) and their offspring (n=25). Serum isoflavone concentrations were higher with TAD soy than TAD casein, but not as high as when monkey chow was fed. Offspring consuming TAD soy had higher serum isoflavone concentrations than adults consuming TAD soy. Female monkeys consuming TAD soy had better glycemic control, as determined by fructosamine concentrations, but no differences in lipids or body weight compared with those consuming diets with TAD casein. Offspring born to dams consuming TAD soy had similar body weights at birth but over a two-year period weighed significantly less, had significantly lower triglyceride concentrations, and like adult females, had significantly lower fructosamine concentrations compared to TAD casein. Glucose tolerance tests in adult females were not significantly different with diet, but offspring eating TAD soy had increased glucose disappearance with overall lower glucose and insulin responses to the glucose challenge compared with TAD casein. Potential reasons for the additional benefits of TAD soy observed in offspring but not in adults may be related to higher serum isoflavone concentrations in offspring, presence of the diet differences throughout more of their lifespan (including gestation), or different tissue susceptibilities in younger animals. Am. J. Primatol. 71:802,811, 2009. © 2009 Wiley-Liss, Inc. [source]

Effects of twin pregnancy and periconceptional undernutrition on maternal metabolism, fetal growth and glucose,insulin axis function in ovine pregnancy