			Home About us Contact

Increased Insulin Sensitivity (increased + insulin_sensitivity)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Effects of short-term training on insulin sensitivity and skeletal muscle glucose metabolism in Standardbred horses

EQUINE VETERINARY JOURNAL, Issue S36 2006
L. STEWART-HUNT
Summary Reasons for performing study: Increased insulin sensitivity occurs after a period of exercise training, but the mechanisms underlying this training-associated increase in insulin action have not been investigated. Objective: To examine the effects of short-term endurance training (7 consecutive days) and a subsequent period of inactivity (5 days) on whole body insulin sensitivity and GLUT-4 protein and the activities of glycogen synthase (GS) and hexokinase (HK) in skeletal muscle. It was hypothesised that training would increase insulin sensitivity in association with increased GLUT-4 protein and activities of GS and HK, but that these changes would be transient, returning to baseline after 5 days of inactivity. Methods: Seven mature Standardbred horses completed training consisting of 7 consecutive days of 45 min of treadmill exercise at a speed that elicited 55% of pretraining maximal aerobic capacity (VO2peak). Insulin sensitivity was determined by rate of glucose disposal (M) during the last 60 min of a 120 min euglycaemic-hyperinsulinaemic clamp (EHC) performed before (-2 days) and at 1 and 6 days following training. VO2peak was measured before (UT) and after (TR) training and the period of inactivity (IA). Results: Training resulted in a 9% increase in mean VO2peak (P<0.05) that was maintained following inactivity (IA). Mean M values were more than 2-fold higher (P<0.05) in TR than in UT. Mean M was also higher (P<0.05) in IA when compared to UT. GLUT-4 protien abundancewas more than 10-fold higher in TR and IA (P<0.001) than in UT. Pre-EHC GS activity and GS fractional velocity were increased (P<0.05) in TR when compared to UT and IA. Pre-EHC HK activity was increased (P<0.05) in IA when compared to UT and TR. Muscle glycogen was 66% lower (P<0.05) in TR than in UT and IA. Conclusions: Short-term training resulted in increases in whole body insulin sensitivity, and GLUT-4 protein content and glycogen synthase activity in skeletal muscle. The enhancements in insulin sensitivity, GLUT-4 protein and glycogen synthase activity were still evident after 5 days of inactivity. Potential relevance: Insulin resistance in equids has been associated with obesity and predisposition to laminitis. Regular physical activity may mitigate risk of these conditions via enhancement of insulin sensitivity and/or control of bodyweight. [source]

Increased insulin sensitivity in young, growth hormone deficient children

CLINICAL ENDOCRINOLOGY, Issue 1 2001
Sandra Husbands
OBJECTIVE Although growth hormone (GH) has well documented insulin antagonistic effects, GH deficient adults often demonstrate insulin resistance. In young GH deficient children, increased susceptibility to hypoglycaemia might indicate increased insulin sensitivity; however, this has not been documented. We therefore determined insulin sensitivity in GH deficient and GH sufficient children. DESIGN AND PATIENTS Prospective study of children undergoing insulin tolerance tests for clinical investigation of GH or cortisol secretion at a regional Paediatric Endocrine/Growth Clinic between October 1986 and December 1997. Ninety-one tests were performed in children with GH deficiency and 142 tests in children with normal GH response to insulin (peak GH , 20 IU/l). MEASUREMENTS The standard insulin tolerance test was modified to permit frequent measurements of glucose (0, 5, 10, 15, 20, 30, 45, 60 and 90 minutes). Rate of log glucose disappearance in the first 15 minutes was calculated as a direct measure of insulin sensitivity. RESULTS GH deficient children were more insulin sensitive than GH sufficient children (P = 0·004) and had lower glucose nadirs post-insulin (P = 0·005). Subgroup analysis revealed that these differences were greater in younger (< 12 years old) or pre/early pubertal children. In 14 prepubertal children, exogenous sex steroid priming resulted in lower insulin sensitivity (P < 0·05) compared to nonprimed tests. CONCLUSIONS Young GH deficient children were more insulin sensitive than children with normal GH secretion. This difference attenuated with age and puberty, possibly secondary to pubertal sex steroids; however, insulin resistance as reported in GH deficient adults, was not observed in adolescents. [source]

Stearoyl-CoA desaturase: a new therapeutic target of liver steatosis

DRUG DEVELOPMENT RESEARCH, Issue 8 2006
Pawel Dobrzyn
Abstract Stearoyl-CoA desaturase (SCD) is the rate limiting enzyme catalyzing the biosynthesis of monounsaturated fatty acids, mainly oleate and palmitoleoate, which are used as substrates for the synthesis of triglycerides, wax esters, cholesterol esters, and phospholipids. Recent studies have shown that SCD1, the main SCD isoform expressed in liver, is a key player in the regulation of lipid metabolism. SCD1 deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice, and attenuates fasting-induced liver steatosis in peroxisome proliferator-activated receptor-, , deficient mice. Consequently, increased SCD activity has been found in humans and animals which accumulate significant amounts of lipids in liver, whereas SCD1 deficiency ameliorates both high-fat diet induced and genetically induced hepatic steatosis. Much evidence indicates that the direct anti-steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and reduced lipid synthesis. In this review we discuss our current understanding of the role of SCD1 in regulation of hepatic lipid partitioning and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non-alcoholic fatty liver disease. Drug Dev. Res. 67:643,650, 2006. © 2006 Wiley-Liss, Inc. [source]

The effect of long-term exercise on glucose metabolism and peripheral insulin sensitivity in Standardbred horses

EQUINE VETERINARY JOURNAL, Issue S36 2006
E. de GRAAF-ROELFSEMA
Summary Reasons for performing study: To study the possible long-term effect of improved glucose tolerance in horses after long-term training, as the impact of exercise training on glucose metabolism is still unclear in the equine species. It is not known whether there is a direct long-term effect of training or if the measurable effect on glucose metabolism is the residual effect of the last exercise session. Objectives: To determine the chronic effect on glucose metabolism and peripheral insulin sensitivity of long-term training in horses by use of the euglycaemic hyperinsulinaemic clamp technique. Methods: Eleven Standardbred horses were acclimatised to running on the high-speed treadmill for 4 weeks (Phase 1) followed by training for 18 weeks with an alternating endurance (, 60% HRmax) high intensity training programme (, 80% HRmax) (Phase 2). Training frequency was 4 days/week. At the end of Phase 1, a euglycaemic hyperinsulinaemic clamp was performed 72 h after the last bout of exercise in all horses. At the end of Phase 2, the horses were clamped 24 h or 72 h after the last bout of exercise. Results: Glucose metabolism rate did not change significantly after 18 weeks of training, measured 72 h after the last exercise bout (0.018 ± 0.009 and 0.022 ± 0.006 mmol/kg bwt/min, respectively). Peripheral insulin sensitivity also did not change significantly following training (7.6 ± 5.7 times 10,6 and 8.0 ± 3.1 times 10,6, respectively). The same measurements 24 h after the last bout of exercise showed no significant differences. Conclusions: Results indicated that long-term training in Standardbreds neither changed glucose metabolism or insulin sensitivity 72 h after the last bout of exercise. Potential relevance: The fact that the beneficial effect of increased insulin sensitivity after acute exercise diminishes quickly in horses and no long-term effects on insulin sensitivity after chronic exercise have as yet been found in horses, implies that exercise should be performed on a regular basis in horses to retain the beneficial effect of improved insulin sensitivity. [source]

Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co-morbidities

JOURNAL OF INTERNAL MEDICINE, Issue 6 2002
O. Ukkola
Abstract.,Ukkola O, Santaniemi M (University of Oulu, Oulu, Finland). Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co-morbidities (Review). J Intern Med 2002; 251: 467,475. Impaired insulin action is important in the pathophysiology of multiple metabolic abnormalities such as obesity and type 2 diabetes. Protein tyrosine phosphatase 1B (PTP1B) is considered a negative regulator of insulin signalling. This is best evidenced by studies on knockout mice showing that lack of PTP1B is associated with increased insulin sensitivity as well as resistance to obesity and in vitro studies whilst studies in animals and humans have given contradictory results. However, several studies support the notion that insulin signalling can be enhanced by the inhibition of PTP1B providing an attractive target for therapy against type 2 diabetes and obesity. In addition, recent genetic studies support the association between PTP1B with insulin resistance. The development of PTP1B inhibitors has already begun although it has become clear that is not easy to find both a selective, safe and effective PTP1B inhibitor. The objective of this paper is to review the current evidence of PTP1B in the pathophysiology of obesity, type 2 diabetes and cancer as well as in the treatment of these disorders. [source]

Altered distribution of adiponectin isoforms in children with Prader,Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones

CLINICAL ENDOCRINOLOGY, Issue 6 2007
Andrea M. Haqq
Summary Objective, Prader,Willi syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinaemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased levels of total and high molecular weight adiponectin and associated with changes in levels of satiety hormones. Design, patients and measurements, We measured total adiponectin and its isoforms [high molecular weight (HMW), middle molecular weight (MMW) and low molecular weight (LMW) adiponectin] and satiety hormones in 14 children with PWS [median age 11·35 years, body mass index (BMI) Z- score 2·15] and 14 BMI-matched controls (median age 11·97 years, BMI Z- score 2·34). Results, Despite comparable BMI Z- scores and leptin levels, the PWS children exhibited lower fasting insulin and HOMA-IR (homeostasis model assessment of insulin resistance) scores compared to obese controls. For any given BMI Z- score, the PWS children showed higher concentrations of fasting total and HMW adiponectin and higher HMW/total adiponectin ratios. The HMW/total adioponectin ratio was preserved in children with PWS at high degrees of obesity. In PWS children, fasting plasma total adiponectin, HMW adiponectin and HMW/total adiponectin ratio correlated negatively with age (P < 0·05), HOMA-IR (P < 0·01), BMI Z- score (P < 0·05), insulin (P < 0·01) and leptin (P < 0·05). In addition to higher fasting ghrelin concentrations, the PWS children showed significantly higher fasting levels of total peptide YY (PYY) and gastric inhibitory polypeptide (GIP) compared to obese controls. Conclusions, Relative to controls of similar age and BMI Z- score, the PWS children had significantly higher levels of total and HMW adiponectin, and increased ratios of HMW/total adiponectin. These findings may explain in part the heightened insulin sensitivity of PWS children relative to BMI-matched controls. [source]