scholarly journals The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hui Wu ◽  
Chunhua Sui ◽  
Hui Xu ◽  
Fangzhen Xia ◽  
Hualing Zhai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Peripheral Tissues ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Glucagon Like Peptide 1

Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose.Results. In the diabetic rats, exenatide reduced the basalRaof glucose (P<0.01) and glycerol (P<0.01) and GNG (P<0.001). During the clamp,Raof glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

Effects of norepinephrine infusion on in vivo insulin sensitivity and responsiveness

1990 ◽  
Vol 259 (2) ◽  
pp. E210-E215 ◽  
Author(s):  
J. R. Lupien ◽  
M. F. Hirshman ◽  
E. S. Horton
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peripheral Tissues

The effect of a continuous infusion of norepinephrine (NE) on glucose disposal in vivo was examined in conscious restrained rats using the euglycemic-hyperinsulinemic clamp technique. NE, 1,000 micrograms.kg-1.day-1 (130 nmol.kg-1.h-1) or vehicle (CO) was infused for 10 days in adult male Sprague-Dawley rats using subcutaneously implanted osmotic minipumps. Body weight and food intake were similar in both groups of animals throughout the study. Fasting basal plasma glucose and insulin concentrations were similar in both groups. However, basal hepatic glucose production (HGP) was increased by NE treatment (9.03 +/- 0.63 vs. 13.20 +/- 1.15 mg.kg-1.min-1, P less than 0.05, CO vs. NE, respectively). Insulin infusions of 2, 6, and 200 mU.kg-1.min-1 suppressed HGP to the same degree in both groups. During 2, 6, and 200 mU.kg-1.h-1 insulin infusions the glucose disposal rate was 65, 60, and 13% greater in NE-treated animals than in controls. Acute beta-adrenergic blockade with propranolol infused at 405 nmol.kg-1.h-1 during the glucose clamps did not normalize glucose disposal. These results demonstrate that chronic NE infusion is associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissues.

scholarly journals Targeted Lipidomics Reveals Associations Between Serum Sphingolipids and Insulin Sensitivity Measured by the Hyperinsulinemic-euglycemic Clamp

2020 ◽  
Author(s):  
Jingya Ye ◽  
Xuan Ye ◽  
Wanzi Jiang ◽  
Chenyan Lu ◽  
Xiaomei Geng ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Metabolic Diseases ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Ionization Mass ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Obesity And Diabetes ◽  
Insight Into

Abstract BackgroundSPs are a group of ubiquitously produced lipids that are structurally involved in cell membranes and include SMs, ceramides, GM3s, etc. Sphingolipids and their substrates and constituents, FAs, are implicated in the pathogenesis of various metabolic diseases associated with obesity, diabetes, and atherosclerosis. Decreased insulin sensitivity or insulin secretion is a multifactorial condition related to obesity and diabetes. Therefore, it is likely that perturbations in serum SPs are associated with diseases. Identifying these associations may reveal useful predictors or give perceptive insight into disease processes. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp, and FPIR was measured to evaluate insulin secretion by the IVGTT. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity based on GIR30 derived from the glucose clamp, which is the standard method, and the cutoff point of GIR30 was set as 5.1 mg/(kg *min).ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. We also found that higher concentrations of serum free FAs (FFA 22:6, FFA 22:5, FFA 18:2, FFA 18:1) were associated with a higher risk of decreased insulin secretion. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria. ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. This suggests that the balance of SMs metabolism, rather than ceramide is correlated with the pathology of insulin resistance, obesity and T2DM. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.

scholarly journals Target lipidomics reveals associations between serum sphingolipids and insulin sensitivity by the glucose clamp

2020 ◽  
Author(s):  
Jingya Ye ◽  
Xuan Ye ◽  
Wanzi Jiang ◽  
Chenyan Lu ◽  
Xiaomei Geng ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Ionization Mass ◽  
Chinese Adults ◽  
Euglycemic Clamp ◽  
Differential Correlation ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Obesity And Diabetes

AbstractBackgroundThis study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity.ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria.ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.

scholarly journals Liraglutide, a Glucagon-Like Peptide-1 Analog, Increased Insulin Sensitivity Assessed by Hyperinsulinemic-Euglycemic Clamp Examination in Patients with Uncontrolled Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hideaki Jinnouchi ◽  
Seigo Sugiyama ◽  
Akira Yoshida ◽  
Kunio Hieshima ◽  
Noboru Kurinami ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Insulin Therapy ◽  
Euglycemic Clamp ◽  
Type 2 Dm ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Aims. Glucagon-like peptide-1 (GLP-1) analog promotes insulin secretion by acting on pancreaticβ-cells. This antihyperglycemic treatment for type 2 diabetes mellitus (DM) has attracted increased clinical attention not only for its antihyperglycemic action but also for its potential extrapancreatic effects. We investigated whether liraglutide, a GLP-1 analog, could enhance insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp in type 2 DM patients.Materials. We prospectively enrolled 31 uncontrolled type 2 DM patients who were hospitalized and equally managed by guided diet- and exercise-therapies and then introduced to either liraglutide- or intensive insulin-therapy for 4 weeks. Insulin sensitivity was assessed by the glucose infusion rate (GIR) using hyperinsulinemic-euglycemic clamp before and after the therapies.Results. Values of HbA1c, postprandial plasma glucose, and body mass index (BMI) were significantly decreased by hospitalized intensive insulin-therapy or liraglutide-therapy. GIR was significantly increased by liraglutide-therapy but not by insulin-therapy, indicating that liraglutide-therapy significantly enhanced insulin sensitivity. BMI decreased during liraglutide-therapy but was not significantly correlated with changes in GIR. Multivariate logistic regression analysis demonstrated that liraglutide-therapy significantly correlated with increased insulin sensitivity in uncontrolled DM patients.Conclusions. Liraglutide may exhibit favorable effects on diabetes control for type 2 DM patients by increasing insulin sensitivity as an extrapancreatic action. Clinical trial registration Unique Identifier isUMIN000015201.

scholarly journals Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep

2006 ◽  
Vol 189 (1) ◽  
pp. 67-75 ◽  
Author(s):  
H Takahashi ◽  
Y Kurose ◽  
S Kobayashi ◽  
T Sugino ◽  
M Kojima ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Infusion ◽  
Glucose Disposal ◽  
Euglycemic Clamp ◽  
Hyperglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Plasma Insulin Levels ◽  
Plasma Gh

The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 ± 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 μg/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44± 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P < 0.01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P < 0.05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.

scholarly journals The Glucagon-Like Peptide-1 Receptor Regulates Endogenous Glucose Production and Muscle Glucose Uptake Independent of Its Incretin Action

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1155-1164 ◽  
Author(s):  
Julio E. Ayala ◽  
Deanna P. Bracy ◽  
Freyja D. James ◽  
Brianna M. Julien ◽  
David H. Wasserman ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Turnover ◽  
Glucose Flux ◽  
Endogenous Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) diminishes postmeal glucose excursions by enhancing insulin secretion via activation of the β-cell GLP-1 receptor (Glp1r). GLP-1 may also control glucose levels through mechanisms that are independent of this incretin effect. The hyperinsulinemic-euglycemic clamp (insulin clamp) and exercise were used to examine the incretin-independent glucoregulatory properties of the Glp1r because both perturbations stimulate glucose flux independent of insulin secretion. Chow-fed mice with a functional disruption of the Glp1r (Glp1r−/−) were compared with wild-type littermates (Glp1r+/+). Studies were performed on 5-h-fasted mice implanted with arterial and venous catheters for sampling and infusions, respectively. During insulin clamps, [3-3H]glucose and 2[14C]deoxyglucose were used to determine whole-body glucose turnover and glucose metabolic index (Rg), an indicator of glucose uptake. Rg in sedentary and treadmill exercised mice was determined using 2[3H]deoxyglucose. Glp1r−/− mice exhibited increased glucose disappearance, muscle Rg, and muscle glycogen levels during insulin clamps. This was not associated with enhanced muscle insulin signaling. Glp1r−/− mice exhibited impaired suppression of endogenous glucose production and hepatic glycogen accumulation during insulin clamps. This was associated with impaired liver insulin signaling. Glp1r−/− mice became significantly hyperglycemic during exercise. Muscle Rg was normal in exercised Glp1r−/− mice, suggesting that hyperglycemia resulted from an added drive to stimulate glucose production. Muscle AMP-activated protein kinase phosphorylation was higher in exercised Glp1r−/− mice. This was associated with increased relative exercise intensity and decreased exercise endurance. In conclusion, these results show that the endogenous Glp1r regulates hepatic and muscle glucose flux independent of its ability to enhance insulin secretion. During increased glucose flux, the glucagon-like peptide-1 receptor regulates endogenous glucose production and muscle glucose uptake independent of its ability to stimulate insulin secretion.

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