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Glucose Regulation (glucose + regulation)

Distribution by Scientific Domains
Medical Sciences82%
Life Sciences13%

Kinds of Glucose Regulation

  • impaired glucose regulation
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    Selected Abstracts

    Role of IGFBP-1 in glucose regulation?

    ACTA PAEDIATRICA, Issue 9 2000
    J Frystyk
    No abstract is available for this article. [source]

    Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects

    DEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006
    Timothy H. Moran
    Abstract Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin,1 (CCK1) receptor. This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior. Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger, preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 360,367, 2006. [source]

    Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation

    DIABETES OBESITY & METABOLISM, Issue 11 2008
    R. R Ortiz-Andrade
    Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source]

    Relationship of glucose regulation to changes in weight: a systematic review and guide to future research

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2010
    Ching-Ju Chiu
    Abstract Although weight gain and obesity are risk factors for poor glucose regulation, the relationship, if any, of glucose regulation to changes in weight is not well understood. The purpose of this study was to conduct a systematic review of research examining the relationship of glucose regulation to changes in weight in human-based studies and to provide guidelines for future research in this area. We searched electronic databases and reference sections of relevant articles, including both diabetic and non-diabetic populations, to locate all the literature published before February 2010, and then conducted a systematic review across studies to compare the research designs and findings. The 22 studies meeting our criteria for review generally supported the relationship of glucose regulation to changes in weight. Three studies reported that poor glucose regulation is associated with weight gain; 12 studies concluded that poor glucose regulation is associated with weight loss; 5 showed complex relationships depending on age, sex, or race/ethnicity; and 2 suggested no relationship. The diverse findings may imply that the direction (negative or positive) of the relationship may depend on specific conditions. More research focused on different subpopulations may provide more definitive information supplemental to the current preliminary findings. Recommendations regarding future research in this particular area are provided in the discussion. Copyright © 2010 John Wiley & Sons, Ltd. [source]

    Impaired glucose regulation and type 2 diabetes in children and adolescents

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2008
    Kerstin Kempf
    Abstract Diabetes mellitus in paediatric patients used to be almost exclusively type 1, but in recent years, case series as well as hospital-based and population-based studies indicated that the number of children and adolescents with type 2 diabetes (T2DM) has been increasing. This development is alarming since T2DM in youth is usually not an isolated condition, but accompanied by other cardiovascular risk factors such as obesity, dyslipidaemia, hypertension and low-grade inflammation. In adults, numerous studies provided detailed data on prevalence, incidence and risk factors for the development of T2DM, but for children and adolescents clinical and experimental data are still rather limited. This review provides an overview about the epidemiology and pathogenesis of T2DM in youth and about impaired glucose regulation as major risk factor for diabetes development with a special focus on the recent literature on clinical and lifestyle-related risk factors. Differences in incidence and prevalence across different populations indicate that ethnic background and genetic pre-disposition may be important risk determinants. In addition, epigenetic factors and foetal programming appear to confer additional risk before birth. Among the environmental and lifestyle-related risk factors there is evidence that obesity, hypercaloric diet, physical inactivity, socio-economic position (SEP), smoking, low-grade inflammation, psychosocial stress and sleeping patterns contribute to the risk for T2DM. However, the assessment of the relevance of risk factors and of incidence or prevalence estimates in youth is complicated by methodological issues that are also discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    The prevalence of depressive symptoms in a white European and South Asian population with impaired glucose regulation and screen-detected Type 2 diabetes mellitus: a comparison of two screening tools

    DIABETIC MEDICINE, Issue 8 2010
    N. Aujla
    Diabet. Med. 27, 896,905 (2010) Abstract Aims, To compare the identification of prevalent depressive symptoms by the World Health Organization-5 Wellbeing Index (WHO-5) and Centre for Epidemiological Studies Depression Scale (CES-D) for South Asian and white European people, male and female, attending a diabetes screening programme, and to explore the adequacy of the screening tools for this population. An additional aim was to further explore associations of depressive symptoms with impaired glucose regulation (IGR) and Type 2 diabetes mellitus (Type2 DM). Methods, Eight hundred and sixty-four white European (40,75 years old) and 290 South Asian people (25,75 years old) underwent an oral glucose tolerance test (OGTT), detailed history and anthropometric measurements and completed the WHO-5 and CES-D. Depressive symptoms were defined by a WHO-5 score , 13, and CES-D score , 16. Results, Unadjusted prevalence of depressive symptoms with the WHO-5, for people with Type2 DM was 42.3% (47.4% in white European; 28.6% in South Asian) and for IGR 30.7% (26% in white European; 45.8% in South Asian). With the CES-D, the prevalence in Type2 DM was 27.2% (25.4% in white European; 31.8% in South Asian) and for IGR 30.7% (27.8% in white European; 40.7% in South Asian). Statistically significant differences in the prevalence of depressive symptoms for sex or ethnicity were not identified. Odds ratios adjusted for age, sex and ethnicity showed no significant association of depression with Type2 DM or IGR, with either WHO-5 or CES-D. Agreement was moderate (, = 0.48, 95% confidence intervals 0.42,0.54), and reduced when identifying depressive symptoms in people with Type2 DM. For this group, a WHO-5 cut-point of , 10 was optimal. Conclusions, Depressive symptoms, identified by WHO-5 or CES-D, were not significantly more prevalent in people with Type2 DM or IGR. The WHO-5 and CES-D differed in their identification of depressive symptoms in people with Type2 DM, though discrepancies between sex and ethnicity were not identified. [source]

    RD Lawrence Lecture 2009 Old genes, new tricks: learning about blood glucose regulation from naturally occurring genetic variation in humans

    DIABETIC MEDICINE, Issue 11 2009
    A. L. Gloyn
    Abstract The study of rare monogenic forms of diabetes and pancreatic B-cell dysfunction provides an unrivalled opportunity to link a specific change in gene function with precise cellular consequences and clinical phenotype in humans. Over the past 20 years there has been considerable success in determining the genetic aetiology of a number of rare monogenic forms of diabetes, which has had a significant impact on both our understanding of normal physiology and on translational medicine. The impact of these discoveries has been substantial, with insights into both developmental biology and normal physiology. There are clear examples where determining the genetic aetiology for individuals with rare monogenic subtypes of diabetes has led to improved treatment. Although formerly in the shadow of the monogenic diabetes field, over the past 3 years there has been staggering progress in our understanding of the genetic basis of Type 2 diabetes. This has been largely as a result of genome-wide association studies and has seen the list of ,diabetes susceptibility genes' increase from three to close to 20. There is now encouraging evidence to support a potential role for genetics in determining the response of individuals with Type 2 diabetes to different therapeutic options. One of the challenges that lies ahead is determining how the non-coding genetic variants exert their pathogenicity. It is possible that parallels can be drawn from functional work on rare regulatory mutations causing monogenic forms of diabetes. However, it is more likely that comprehensive approaches will be necessary. [source]

    Impaired glucose regulation, elevated glycated haemoglobin and cardiac ischaemic events in vascular surgery patients

    DIABETIC MEDICINE, Issue 3 2008
    H. H. H. Feringa
    Abstract Aims Cardiac morbidity and mortality is high in patients undergoing high-risk surgery. This study investigated whether impaired glucose regulation and elevated glycated haemoglobin (HbA1c) levels are associated with increased cardiac ischaemic events in vascular surgery patients. Methods Baseline glucose and HbA1c were measured in 401 vascular surgery patients. Glucose < 5.6 mmol/l was defined as normal. Fasting glucose 5.6,7.0 mmol/l or random glucose 5.6,11.1 mmol/l was defined as impaired glucose regulation. Fasting glucose , 7.0 or random glucose , 11.1 mmol/l was defined as diabetes. Perioperative ischaemia was identified by 72-h Holter monitoring. Troponin T was measured on days 1, 3 and 7 and before discharge. Cardiac death or Q-wave myocardial infarction was noted at 30-day and longer-term follow-up (mean 2.5 years). Results Mean (± sd) level for glucose was 6.3 ± 2.3 mmol/l and for HbA1c 6.2 ± 1.3%. Ischaemia, troponin release, 30-day and long-term cardiac events occurred in 27, 22, 6 and 17%, respectively. Using subjects with normal glucose levels as the reference category, multivariate analysis revealed that patients with impaired glucose regulation and diabetes were at 2.2- and 2.6-fold increased risk of ischaemia, 3.8- and 3.9-fold for troponin release, 4.3- and 4.8-fold for 30-day cardiac events and 1.9- and 3.1-fold for long-term cardiac events. Patients with HbA1c > 7.0% (n = 63, 16%) were at 2.8-fold, 2.1-fold, 5.3-fold and 5.6-fold increased risk for ischaemia, troponin release, 30-day and long-term cardiac events, respectively. Conclusions Impaired glucose regulation and elevated HbA1c are risk factors for cardiac ischaemic events in vascular surgery patients. [source]

    Hyperglycaemia and cardiovascular disease

    JOURNAL OF INTERNAL MEDICINE, Issue 2 2007
    M. Bartnik
    Abstract. Coronary artery disease and type 2 diabetes are chronic diseases of substantial and growing prevalence. Their coincidence is common, markedly enhancing mortality and morbidity. The risk for cardiovascular disease increases along a spectrum of blood glucose concentrations already apparent at levels regarded as normal. Accordingly, strategies for the early detection of glucometabolic disturbances are needed to find ways to prevent the occurrence of cardiovascular complications or to treat them already at an early stage. More specifically, abnormal glucose tolerance is almost twice as common amongst patients with a myocardial infarction as in population-based controls and a normal glucose regulation is indeed less common than abnormal glucose metabolism also amongst patients with stable coronary artery disease. Already an abnormal glucose tolerance is a strong risk factor for future cardiovascular events after an acute myocardial infarction. An oral glucose tolerance test should, therefore, be a part of the evaluation of total risk in all patients with coronary artery disease. As glucose disturbances are common and easy to detect, they may be suitable targets for novel secondary preventive efforts. [source]

    Blood Glucose Level, Alcohol Heavy Drinking, and Alcohol Craving During Treatment for Alcohol Dependence: Results From the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study

    ALCOHOLISM, Issue 9 2009
    Lorenzo Leggio
    Background:, Heavy drinking may increase blood glucose levels. Moreover, in alcohol-dependent subjects, glucose may play a putative role in alcohol preference. Methods:, This study investigated the relationship between blood glucose levels and both alcohol heavy drinking and craving in alcohol-dependent subjects participating in the COMBINE Study. The primary objective was to evaluate the relationship between baseline (pretreatment) glucose levels and percentage of heavy drinking day (PHDD) during treatment. The secondary objective was to evaluate the relationship between glucose levels, baseline PHDD, and craving measured by the Obsessive Compulsive Drinking Scale (OCDS). Results:, This analysis consisted of 1,324 participants. Baseline glucose levels were significantly and positively associated with PHDD during treatment [F(1, 1225) = 5.21, p = 0.023], after controlling for baseline PHDD [F(1, 1225) = 36.25, p < 0.0001], gender [F (1, 1225) = 3.33, p = 0.07], and body mass index (BMI) [F(1, 1225) = 0.31, p = 0.58]. Higher glucose levels at baseline were associated with a higher percentage of PHDD at pretreatment [F(1, 1304) = 5.96, p = 0.015], after controlling for gender [F(1, 1304) = 0.29, p = 0.59] and BMI [F(1, 1304) = 0.90, p = 0.34]. Glucose was not significantly associated with the OCDS total score [F(1, 1304) = 0.12, p = 0.73], the OCDS Obsessive subscale [F(1, 1304) = 0.35, p = 0.56], or the OCDS Compulsive subscale [F(1, 1304) = 1.19, p = 0.28] scores, after controlling for gender and BMI. Discussion:, A link between pretreatment glucose levels and heavy drinking during treatment was found, suggesting a role of glucose in predicting heavy alcohol consumption. Although caution is needed in the interpretation of these results, elevated glucose and heavy drinking may be affected by a common mechanism and manipulations affecting glucose regulation may influence alcohol consumption. [source]

    Diabetes, pre-diabetes and associated risks on Minnesota code-indicated major electrocardiogram abnormality among Chinese: a cross-sectional diabetic study in Fujian province, southeast China

    OBESITY REVIEWS, Issue 4 2009
    L. Lin
    Summary The goal of this study was to determine the prevalence of diabetes mellitus (DM), impaired glucose regulation (IGR) and related metabolic disorders (overweight, obesity and hypertension) in a Chinese population (20,74 years old). An additional goal was to investigate the relationship between glucose metabolism and the Minnesota code-indicated major abnormal electrocardiogram (MA-ECG). There were 3960 individuals selected from urban and rural areas of Fujian, China from July 2007 to May 2008 by multistage-stratified sampling. Ultimately, data from 3208 subjects (20,74 years old) were analysed (including physical measurements, blood biochemical analysis, oral glucose tolerance test and 12-lead resting ECG). According to World Health Organization diagnostic criteria, the prevalence rates of DM and IGR were 9.51% (male, 10.08%; female, 9.14%) and 14.40% (male, 14.48%; female, 14.35%) respectively. Newly diagnosed DM was found in 53.44% of the diabetic subjects. Based on the 2000 China census, the age-standardized prevalence rates of DM and IGR were 7.19% (male, 7.74%; female, 6.61%) and 11.96 % (male, 12.35%; female, 11.56%) respectively. The age-standardized prevalence rates of DM and IGR in urban areas (7.74% and 12.97% respectively) were slightly but no significantly higher than in rural areas (6.67%, 10.86%). The prevalence rates of overweight, obesity and hypertension were 25.50%, 3.52% and 28.52% respectively (age- and sex- standardized rates: 23.69%, 3.02 % and 22.45 %). After adjusting for other confounding risk factors, multiple logistic regression analysis showed that DM and impaired glucose tolerance were independent risk factors for MA-ECG. Non-diabetic subjects with increased 30-min plasma glucose (PG) after an oral glucose load had a higher risk of MA-ECG after adjusting for other risk factors, especially in those with normal glucose tolerance but with 30-min PG , 7.8 mmol L,1 (odds ratio = 1.371 [1.055,1.780]). The prevalence rates of DM and IGR as well as other metabolic disorders have increased dramatically in the last decade in China, especially in rural areas, with many undiagnosed cases of DM. Even slightly elevated PG levels may predict early cardiovascular events. [source]

    Profound changes in the GH,IGF-I system in adolescent girls with IDDM: can IGFBP1 be used to reflect overall glucose regulation?

    PEDIATRIC DIABETES, Issue 3 2000
    MU Halldin
    Disturbances in the relations between insulin, growth hormone (GH) and insulin-like growth factor I (IGF-I) may be a major cause behind deteriorated metabolic control in adolescent girls with type I diabetes. These patients have increased GH secretion and low IGF-I concentrations. The aim of this study was to identify possible endocrine mechanisms behind good and poor glycaemic control in such girls, focusing on the insulin,GH,IGF-I axis. Ten girls with well-controlled insulin-dependent diabetes mellitus (IDDM), hemoglobin A1c (HbA1c) 6.5±0.4% (normal range 3.9,5.2%) and nine healthy controls were investigated and compared with 11 girls with poor glucose regulation, HbA1c 10.9±0.4%, and their corresponding controls. Serum profiles of glucose, insulin, GH and IGF-binding protein 1 (IGFBP1) were analysed in addition to IGF-I and HbA1c. Two interesting observations were made. GH concentrations were equally elevated in the two diabetic groups regardless of metabolic control (mean 24 h GH , girls with poorly controlled diabetes 10.0±1.0 mU/L vs 9.8±1.7 , girls with well-controlled diabetes; p=ns). Likewise, the IGF-I concentrations were reduced to the same extent (233±19 vs 242±23 ,g/L; p=0.75). Secondly, despite similar insulin concentrations (mean 24 h insulin , girls with poorly controlled diabetes 22.9±2.6 and girls with well-controlled diabetes 27.3±2.9 mU/L, respectively; p=0.26), there was a marked difference in IGFBP1 concentrations between the two groups with IDDM (mean IGFBP1 , girls with poorly controlled diabetes 70.5±9.1 ,g/L vs girls with well-controlled diabetes 28.6±3.3; p<0.001). Despite equally elevated GH concentrations that may induce insulin resistance, the markedly lower concentrations of IGFBP1 in the well-controlled group indicate a higher hepatic insulin sensitivity in these girls compared with those with a poor control. Furthermore, in spite of similar total IGF-I concentrations, the lower IGFBP1 concentrations may result in higher IGF-I bioactivity in the well-controlled group. This may be reflected in better growth of the well-controlled group whose height of 168.7±0.9 vs 163.6±1.2 cm was significantly different (p<0.004). IGFBP1 may be a marker of overall insulinization in adolescents with type 1 diabetes, independent of the absolute insulin dose used for therapy. [source]

    Pleiotropic effects on subclasses of HDL, adiposity, and glucose metabolism in adult Alaskan Eskimos

    AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2010
    M. Elizabeth Tejero
    The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 ± 0.11 for LDL2 (intermediate) and 0.89 ± 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source]

    High prevalence of diabetes and pre-diabetes in adults with Williams syndrome,

    AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2010
    B.R. Pober
    Abstract A standard oral glucose tolerance test (OGTT) was administered to 28 adults with Williams syndrome (WS). Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre-diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age,gender,BMI matched controls, though the glucose area under the curve was greater in the WS subjects. HbA1c levels were not as reliable as the OGTT in diagnosing the presence of diabetes. Given the high prevalence of impaired glucose regulation, adults with WS should be screened for diabetes, and when present should be treated in accordance with standard medical practice. Hemizygosity for a gene mapping to the Williams syndrome chromosome region (WSCR) is likely the major factor responsible for the high frequency of diabetes in WS. Syntaxin-1A is a prime candidate gene based on its location in the WSCR, its role in insulin release, and the presence of abnormal glucose metabolism in mouse models with aberrantly expressed Stx-1a. © 2010 Wiley-Liss, Inc. [source]

    Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to ,-adrenergic stimulation

    THE JOURNAL OF PHYSIOLOGY, Issue 15 2010
    Jennifer C. Richards
    Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance-trained adults. Accordingly, we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) SIT (n= 12): six sessions of repeated (4,7) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days; (2) sedentary control (n= 10); (3) single-bout SIT (n= 9): one session of 4 × 30 s cycle ergometer sprints. Insulin sensitivity was determined (hyperinsulinaemic euglycaemic clamp) prior to and 72 h following each intervention. Compared with baseline, and sedentary and single-bout controls, SIT increased insulin sensitivity (glucose infusion rate: 6.3 ± 0.6 vs. 8.0 ± 0.8 mg kg,1 min,1; mean ±s.e.m.; P= 0.04). In a separate study, we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor (,-AR) stimulation, an important determinant of energy balance. Compared with baseline, and sedentary and single-bout control groups, SIT did not affect resting energy expenditure (EE: ventilated hood technique; 6274 ± 226 vs. 6079 ± 297 kJ day,1; P= 0.51) or the thermogenic response to isoproterenol (6, 12 and 24 ng (kg fat-free mass),1 min,1: %,EE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P= 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial-derived factor, non-esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to ,-AR stimulation. [source]

    Pharmacodynamics of glucose regulation by methylprednisolone.

    BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009

    Abstract Mechanisms related to the adverse effects of corticosteroids on glucose homeostasis were studied. Five groups of adrenalectomized (ADX) rats were given methylprednisolone (MPL) intravenously at 10 and 50,mg/kg, or a continuous 7 day infusion at rates of 0, 0.1, 0.3,mg/kg/h via subcutaneously implanted Alzet mini-pumps. Plasma concentrations of MPL, glucose and insulin were determined at various time points up to 72,h after injection or 336,h after infusion. The pharmacokinetics of MPL was captured with a two-compartment model. The Adapt II software was used in modeling. Injection of MPL caused a temporary glucose increase over 6,h by stimulating gluconeogenesis. The glucose changes stimulated pancreatic ,-cell secretion yielding a later insulin peak at around 10,h. In turn, insulin can stimulate glucose disposition. However, long-term MPL treatment caused continuous hyperglycemia during and after infusion. Insulin was increased during infusion, and immediately returned to baseline after the infusion was terminated, despite the almost doubled glucose concentration. A disease progression model incorporating the reduced endogenous glucose disposition was included to capture glucose homeostasis under different treatments. The results exemplify the importance of the steroid dosing regimen in mediating pharmacological and adverse metabolic effects. This mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model quantitatively describes the induction of hyperglycemia and provides additional insights into metabolic disorders such as diabetes. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Pharmacodynamics of glucose regulation by methylprednisolone.

    BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009
    II. normal rats
    Abstract A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50,mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3,mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72,h after injection and 336,h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline caused by handling, which was captured by a circadian harmonic secretion rate with an increasing mesor. All drug treatments caused CST suppression. Injection of MPL caused temporary increases in glucose over 4,h. Insulin secretion was thereby stimulated yielding a later peak around 6,h. In turn, insulin can normalize glucose. However, long-term dosing caused continuous hyperglycemia during and after infusion. Hyperinsulinemia was achieved during infusion, but diminished immediately after dosing despite the high glucose concentration. The effects of CST and MPL on glucose production were described with a competitive stimulation function. A disease progression model incorporating reduced endogenous glucose uptake/utilization was used to describe glucose metabolism under different treatments. The results exemplify the roles of endogenous and exogenous hormones in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is valuable for quantitating diabetogenic effects of corticosteroid treatments and provides mechanistic insights into the hormonal control of the metabolic system. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Development and characterization of a tissue engineered pancreatic substitute based on recombinant intestinal endocrine L-cells

    BIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009
    Heather Bara
    Abstract A tissue engineered pancreatic substitute (TEPS) consisting of insulin-producing cells appropriately designed and encapsulated to support cellular function and prevent interaction with the host may provide physiological blood glucose regulation for the treatment of insulin dependent diabetes (IDD). The performance of agarose-based constructs which contained either a single cell suspension of GLUTag-INS cells, a suspension of pre-aggregated GLUTag-INS spheroids, or GLUTag-INS cells on small intestinal submucosa (SIS), was evaluated in vitro for total cell number, weekly glucose consumption and insulin secretion rates (GCR and ISR), and induced insulin secretion function. The three types of TEPS studied displayed similar number of cells, GCR, and ISR throughout 4 weeks of culture. However, the TEPS, which incorporated SIS as a substrate for the GLUTag-INS cells, was the only type of TEPS tested which was able to retain the induced insulin secretion function of non-encapsulated GLUTag-INS cells. Though improvements in the expression level of GLUTag-INS cells and/or the number of viable cells contained within the TEPS are needed for successful treatment of a murine model of IDD, this study has revealed a potential method for promoting proper cellular function of recombinant L-cells upon incorporation into an implantable three-dimensional TEPS. Biotechnol. Bioeng. 2009;103: 828,834. © 2009 Wiley Periodicals, Inc. [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]

    Prevalence and associated factors of restless legs in a 57-year-old urban population in northern Finland

    ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010
    A. K. Juuti
    Juuti AK, Läärä E, Rajala U, Laakso M, Härkönen P, Keinänen-Kiukaanniemi S, Hiltunen L. Prevalence and associated factors of restless legs in a 57-year-old urban population in northern Finland. Acta Neurol Scand: 2010: 122: 63,69. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, We examined the prevalence and associated factors of restless legs syndrome (RLS) in a 57-year-old unselected urban population in northern Finland. Methods,,, A health survey was conducted in 2002 that targeted persons born in 1945 and residing in the city of Oulu on 31 December, 2001. Their history of RLS, coronary heart disease (CHD), daytime sleepiness, depressive symptoms and snoring was assessed by means of questionnaires. Results,,, Altogether 995 of 1332 eligible subjects (74%) participated (556 women, 439 men). The overall prevalence of RLS , 1 per week was 20% in women and 15% in men. In the fitted multiple logistic regression model, RLS was found to be associated with female gender (OR 1.64, 95% CI 0.98,2.72), CHD (OR 2.92, 95% CI 1.18,7.23), daytime sleepiness (OR 2.12, 95% CI 1.32,3.41), moderately elevated (31,45) or high (46,65) Zung sum scores (OR 1.95, 95% CI 1.09,3.48 and OR 3.67, 95% CI 1.71,7.90, respectively), antidepressant medication (OR 2.10, 95% CI 1.06,4.19) and arthropathy (OR 1.69, 95% CI 1.04,2.72). Insufficient evidence was found of an association between RLS and type 2 diabetes or impaired glucose regulation. Conclusions,,, Restless legs syndrome is fairly common in subjects aged 57 years. A particularly strong positive association was observed between RLS and depressive symptoms and CHD. [source]

    The circulating IGF system and its relationship with 24-h glucose regulation and insulin sensitivity in healthy subjects

    CLINICAL ENDOCRINOLOGY, Issue 6 2003
    Jan Frystyk
    Summary objective and design It has been suggested that circulating free IGF-I participates in glucose homeostasis and that IGFBP-1 reflects changes in insulin sensitivity. To study this further, we examined 10 healthy, nonobese subjects under standardized conditions for 24 h with and without an intravenous infusion of glucose, the latter in order to augment insulin sensitivity. Serum was collected every 2 h for analysis of free and total IGFs, IGFBP-1, , 2 and , 3 and the acid labile subunit (ALS). Insulin sensitivity was estimated at the end of each 24-h study period by use of the hyperinsulinaemic euglycaemic clamp technique. results Glucose infusion resulted in mild hyperglycaemia (P < 0·0001), a reduction in IGFBP-1 by approximately 40% (P < 0·0003), and increased insulin and C-peptide levels (P < 0·0001). Glucose infusion also increased insulin sensitivity (P < 0·003). However, despite the reduction in IGFBP-1, glucose infusion did not increase free IGF-I over the control level, and free IGF-II was slightly reduced (P < 0·02). Irrespective of glucose infusion, free IGF-I and -II remained stable during daytime (i.e. they were unresponsive to meal-related changes in plasma glucose), but both free fractions decreased during the night, reaching nadir at 04·00 h. None of the other members of the IGF system showed any relationship with plasma glucose levels. Finally, we failed to observe any relationship between changes in insulin sensitivity and the circulating IGF system. conclusion We found no evidence that the circulating IGF system is involved in meal-related blood glucose regulation or that it reflects short-term changes in insulin sensitivity in healthy, nonobese subjects. However, we cannot preclude that the observed changes in circulating IGFBP-1 may affect the glucose-lowering effect of IGF-I and -II at the local tissue level. [source]