Comparison of the rapid insulin sensitivity test (RIST), the insulin tolerance test (ITT), and the hyperinsulinemic euglycemic clamp (HIEC) to measure insulin action in rats

2002 ◽  
Vol 80 (8) ◽  
pp. 811-818 ◽  
Author(s):  
Maria A.G Reid ◽  
Martin G Latour ◽  
Dallas J Legare ◽  
Na Rong ◽  
W Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Initial Response ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Sensitivity Test ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Insulin Tolerance

The objective was to compare the ability of the rapid insulin sensitivity test (RIST), the hyperinsulinemic euglycemic clamp (HIEC), and the insulin tolerance test (ITT) to detect hepatic insulin sensitizing substance (HISS) dependent insulin action. HISS action was augmented by feeding and inhibited by fasting, blockade of hepatic nitric oxide synthase, or blockade of hepatic muscarinic cholinergic receptors. A significant correlation was found between the RIST index and ITT nadir (r2 = 0.84) but not between the glucose infusion rate of the HIEC and RIST index. There was, however, a relationship between the RIST index and the initial response during the HIEC. Use of the HIEC resulted in HISS-dependent insulin resistance in both conscious and anesthetized animals. We concluded that since the RIST and ITT were comparable in quantifying both HISS-dependent and HISS-independent insulin action, the RIST was validated against this standard. The observation that the HIEC is capable of detecting HISS action in the first rising slope of the test but not at the end of the test and that HISS release is fully blocked after the conclusion of the HIEC raises concerns about the use of the commonly used HIEC.Key words: HISS, insulin resistance, insulin sensitivity tests.

scholarly journals Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

2013 ◽  
Vol 2 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Esben Thyssen Vestergaard ◽  
Morten B Krag ◽  
Morten M Poulsen ◽  
Steen B Pedersen ◽  
Niels Moller ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Binding Protein ◽  
Human Subjects ◽  
Retinol Binding Protein ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Retinol Binding Protein 4 ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

ObjectiveSupraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.Materials and methodsTo study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.ResultsGhrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.Conclusionsi) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

Abstract 17025: Myeloid Rage Protects From Insulin Resistance in Mice Fed High Fat Diet

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Robin Wilson ◽  
Laura Frye ◽  
Ravichandran Ramasamy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
Double Knockout ◽  
Euglycemic Clamp ◽  
Insulin Resistant ◽  
Hyperinsulinemic Euglycemic Clamp

Introduction: Obesity is a major global health problem, with over one third of adults in the US classified as obese. Obesity often leads to a state of insulin resistance (IR), type 2 diabetes (T2D) and its complications. We previously showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and IR, as whole body and adipocyte-specific Ager (gene encoding RAGE) deleted mice fed a high fat diet (HFD) were significantly protected from weight gain and IR. Here, we hypothesize that myeloid RAGE contributed to IR upon HFD feeding. Methods: We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager flox/flox and adipocyte and myeloid-specific (Double Knockouts) AdipoQCre(-/+)LyzMCre(+/+).Ager flox/flox deletion of Ager and LysMCre mice were used as control. Mice were fed either standard chow (LFD) or HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and composition, glucose and insulin sensitivity and whole body glucose metabolism by hyperinsulinemic-euglycemic clamp studies. Results: After 3 months HFD, there were no significant differences in body mass, body composition, food intake, energy expenditure and physical activity of the MDR mice vs. controls. Similar findings were observed in mice fed LFD. However, surprisingly, in HFD-fed mice, insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies showed decreased insulin sensitivity and insulin action in the MDR vs. control mice, indicating that the MDR mice were more insulin resistant. The Double Knockout (myeloid/adipocyte) Cre (+) mice were more glucose tolerant and insulin sensitive compared to MDR mice, showing that deletion of Ager in the adipocytes rescued the adverse effects of Ager deletion in myeloid cells. Conclusions: Myeloid Ager protects from IR in mice fed HFD. Furthermore, in MDR mice, concomitant adipocyte-specific deletion of Ager rescues these mice from IR and, at the same time, reduces HFD-induced adiposity. The mechanisms underlying these findings are under active investigation.

scholarly journals Rac1 in Muscle Is Dispensable for Improved Insulin Action After Exercise in Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3009-3015 ◽  
Author(s):  
Lykke Sylow ◽  
Lisbeth L. V. Møller ◽  
Gommaar D'Hulst ◽  
Peter Schjerling ◽  
Thomas E. Jensen ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Action ◽  
Tolerance Test ◽  
Whole Body ◽  
Wild Type ◽  
Acute Bout ◽  
Insulin Resistant ◽  
Insulin Tolerance ◽  
Rac1 Activity ◽  
Sensitizing Effect

Exercise has a potent insulin-sensitivity enhancing effect on skeletal muscle, but the intracellular mechanisms that mediate this effect are not well understood. In muscle, Ras-related C3 botulinum toxin substrate 1 (Rac1) regulates both insulin- and contraction-stimulated glucose transport and is dysregulated in insulin resistant muscle. However, whether Rac1 is involved in mediating enhanced insulin sensitivity after an acute bout of exercise is unresolved. To address this question, we investigated after exercise whole-body (insulin tolerance test) as well as muscle (insulin-stimulated 2-deoxyglucose transport in isolated soleus muscle) insulin sensitivity in inducible muscle-specific Rac1 knockout (mKO) and wild-type (WT) littermate mice. Previous exercise enhanced whole-body insulin sensitivity by 40% in WT mice and rescued the insulin intolerance in Rac1 mKO mice by improving whole-body insulin sensitivity by 230%. In agreement, previous exercise significantly improved insulin sensitivity by 20% in WT and by 40% in Rac1 mKO soleus muscles. These findings suggest that muscle Rac1 is dispensable for the insulin sensitizing effect of exercise. Moreover, insulin resistance in Rac1 mKO mice can be completely normalized by previous exercise explaining why insulin resistant patients can increase insulin action with exercise despite dysfunctional Rac1 activity in muscle.

Evaluation of different methods for assessment of insulin sensitivity in Göttingen minipigs: introduction of a new, simpler method

2009 ◽  
Vol 297 (4) ◽  
pp. R1195-R1201 ◽  
Author(s):  
Berit Christoffersen ◽  
Ulla Ribel ◽  
Kirsten Raun ◽  
Valeria Golozoubova ◽  
Giovanni Pacini
Keyword(s):  
Insulin Sensitivity ◽  
Cell Function ◽  
High Energy ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Oral Glucose ◽  
Β Cell ◽  
Simple Index ◽  
Insulin Tolerance ◽  
Β Cell Function

The use of animal models in diabetes research requires reliable tests for evaluation of insulin sensitivity and β-cell function. Minipigs are being increasingly used in metabolic research, and the aim of this study was to compare different tests and indexes for evaluation of insulin sensitivity and β-cell function in Göttingen minipigs. Hyperinsulinemic, isoglycemic clamp, intravenous (IVGTT) and oral glucose tolerance tests (OGTT), and a modified insulin tolerance test were performed in minipigs fed either low- or high-energy diet. Furthermore, the reproducibility of IVGTT-derived parameters was assessed. Previously described insulin sensitivity indexes [steady-state glucose infusion rate/glucose concentration/insulin concentration from clamp (M/G/I); oral glucose insulin sensitivity (OGIS) and ISIcomp from OGTT; SI from minimal model analysis of IVGTT; and quantitative insulin sensitivity check index from fasting values] were calculated together with an insulin sensitivity index from the modified insulin tolerance test (ISIITT) and a new simple index (S2) derived from the first 30 min of the IVGTT. β-Cell function was assessed from the IVGTT and the OGTT. Reproducibility of the IVGTT-derived parameters was calculated as median intraindividual coefficient of variation (CV%).M/G/I correlated significantly only with S2 ( P < 0.05, r = 0.54). S2 furthermore correlated with SI ( P < 0.001, r = 0.81), ISIITT ( P < 0.001, r = 0.57), and the two indexes from OGTT, ISIcomp ( P < 0.001, r = 0.78) and OGIS ( p < 0.05, r = 0.48). No correlation was found between β-cell function indexes from OGTT and IVGTT. The median CV% of the new S2 index was 13. In conclusion, the new simple index of insulin sensitivity, S2, was revealed to be useful for evaluation of insulin sensitivity in pigs.

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