scholarly journals Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet

2008 ◽  
Vol 294 (1) ◽  
pp. E142-E147 ◽  
Author(s):  
Edwin T. Parlevliet ◽  
Annemieke C. Heijboer ◽  
Janny P. Schröder-van der Elst ◽  
Louis M. Havekes ◽  
Johannes A. Romijn ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Insulin Levels ◽  
Insulin Resistant

We evaluated the acute effects of OXM on glucose metabolism in diet-induced insulin-resistant male C57Bl/6 mice. To determine the effects on glucose tolerance, mice were intraperitoneally injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle prior to an ip glucose tolerance test. OXM (0.75 nmol/h) or vehicle was infused during a hyperinsulinemic euglycemic clamp to quantify insulin action on glucose production and disposal. OXM dose-dependently improved glucose tolerance as estimated by AUC for glucose (OXM: 7.5 nmol, 1,564 ± 460, P < 0.01; 2.5 nmol, 1,828 ± 684, P < 0.01; 0.75 nmol, 2,322 ± 303, P < 0.05; control: 2,790 ± 222 mmol·l−1·120 min). Insulin levels in response to glucose administration were higher in 7.5 nmol OXM-treated animals compared with controls. In basal clamp conditions, OXM increased EGP (82.2 ± 14.7 vs. 39.9 ± 5.7 μmol·min−1·kg−1, P < 0.001). During insulin infusion, insulin levels were twice as high in OXM-treated mice compared with controls (10.6 ± 2.8 vs. 4.4 ± 2.2 ng/ml, P < 0.01). Consequently, glucose infusion rate (118.6 ± 30.8 vs. 38.8 ± 26.4 μl/h, P < 0.001) and glucose disposal (88.1 ± 13.0 vs. 45.2 ± 6.9 μmol·min−1·kg−1, P < 0.001) were enhanced in mice that received OXM. In addition, glucose production was more suppressed during OXM infusion (35.7 ± 15.5 vs. 15.8 ± 11.4% inhibition, P < 0.05). However, if these data were expressed per unit concentration of circulating insulin, OXM did not affect insulin action on glucose disposal and production. These results indicate that OXM beneficially affects glucose metabolism in diet-induced insulin-resistant C57Bl/6 mice. It ameliorates glucose intolerance, most likely because it elevates glucose-induced plasma insulin concentrations. OXM does not appear to impact on insulin action.

Glucose tolerance and insulin action in healthy centenarians

1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects

2002 ◽  
Vol 282 (6) ◽  
pp. E1360-E1368 ◽  
Author(s):  
Thongchai Pratipanawatr ◽  
Wilailak Pratipanawatr ◽  
Clifford Rosen ◽  
Rachele Berria ◽  
Mandeep Bajaj ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Control Subjects ◽  
Igf I ◽  
Plasma Ffa ◽  
Type 2 Diabetic

The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU · kg−1 · min−1) clamp and a two-step euglycemic IGF-I (26 and 52 pmol · kg−1 · min−1) clamp with [3-3H]glucose, [1-14C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (Rd) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of Rd (second clamp step) in response to both insulin and IGF-I was reduced by ∼40–50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin ( P < 0.01–0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects ( P < 0.05–0.01). Conclusions: 1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia

2006 ◽  
Vol 290 (1) ◽  
pp. E47-E53 ◽  
Author(s):  
D. N. Reeds ◽  
K. E. Yarasheski ◽  
L. Fontana ◽  
W. T. Cade ◽  
E. Laciny ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
High Dose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Stimulation Of

Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride >250 mg/dl and HDL <45mg/dl; n = 12), HIV-infected men without dyslipidemia (HIV w/o DL; n = 12), and healthy men ( n = 6). Basal rates of glucose production (glucose Ra), glucose disposal (glucose Rd), and lipolysis (palmitate Ra) were similar between groups. The relative suppression of glucose Ra(63 ± 4, 77 ± 2, and 78 ± 3%, P = 0.008) and palmitate Ra(49 ± 4, 63 ± 3, and 68 ± 3%, P = 0.005) during low-dose insulin infusion (plasma insulin ∼30 μU/ml), and the relative stimulation of glucose Rd(214 ± 21, 390 ± 25, and 393 ± 46%, P = 0.001) during high-dose insulin infusion (plasma insulin ∼75 μU/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose Racorrelated with plasma adiponectin ( r = 0.44, P = 0.02) and inversely with plasma IL-6 ( r = −0.49, P < 0.001). Stimulation of glucose Rdcorrelated directly with adiponectin ( r = 0.48, P < 0.01) and inversely with IL-6 ( r = −0.49, P = 0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multiorgan insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action.

scholarly journals A primary defect in glucose production alone cannot induce glucose intolerance without defects in insulin secretion

2011 ◽  
Vol 210 (3) ◽  
pp. 335-347 ◽  
Author(s):  
Salvatore P Mangiafico ◽  
Shueh H Lim ◽  
Sandra Neoh ◽  
Helene Massinet ◽  
Christos N Joannides ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Genetic Model ◽  
Genetic Defect ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Transgenic Rats ◽  
Primary Defect

Increased glucose production is associated with fasting hyperglycaemia in type 2 diabetes but whether or not it causes glucose intolerance is unclear. This study sought to determine whether a primary defect in gluconeogenesis (GNG) resulting in elevated glucose production is sufficient to induce glucose intolerance in the absence of insulin resistance and impaired insulin secretion. Progression of glucose intolerance was assessed in phosphoenolpyruvate carboxykinase (PEPCK) transgenic rats, a genetic model with a primary increase in GNG. Young (4–5 weeks of age) and adult (12–14 weeks of age) PEPCK transgenic and Piebald Virol Glaxo (PVG/c) control rats were studied. GNG, insulin sensitivity, insulin secretion and glucose tolerance were assessed by intraperitoneal and intravascular substrate tolerance tests and hyperinsulinaemic/euglycaemic clamps. Despite elevated GNG and increased glucose appearance, PEPCK transgenic rats displayed normal glucose tolerance due to adequate glucose disposal and robust glucose-mediated insulin secretion. Glucose intolerance only became apparent in the PEPCK transgenic rats following the development of insulin resistance (both hepatic and peripheral) and defective glucose-mediated insulin secretion. Taken together, a single genetic defect in GNG leading to increased glucose production does not adversely affect glucose tolerance. Insulin resistance and impaired glucose-mediated insulin secretion are required to precipitate glucose intolerance in a setting of chronic glucose oversupply.

Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and hypoglycemic insulin clamps

1997 ◽  
Vol 272 (4) ◽  
pp. E530-E542 ◽  
Author(s):  
B. A. Zinker ◽  
R. G. Allison ◽  
D. B. Lacy ◽  
D. H. Wasserman
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Vena Cava ◽  
External Iliac Artery ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Marked Rise ◽  
Cortisol Responses ◽  
Exercise Induced

Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the interaction of exercise, insulin, and hypoglycemia at rest and during exercise in the dog. Sampling (artery and portal, hepatic, and iliac veins) and infusion (vena cava) catheters and a flow probe (external iliac artery) were implanted surgically >16 days before study. After an 18-h fast and an 80-min tracer equilibration period, dogs were studied in the basal state (t = -40 to 0 min) and during a moderate treadmill exercise (t = 0-150 min) period or an equivalent duration sedentary period. Insulin was infused at 1 mU x kg(-1) x min(-1) from t = 0-150 min. In one group of sedentary (n = 7) and one group of exercised (n = 6) dogs, glucose was clamped at basal during the insulin infusion. In another group of sedentary (n = 6) and another group of exercised (n = 6) dogs, arterial glucose was clamped at hypoglycemic levels (approximately 65 mg/dl) during the insulin infusion. Arteriovenous difference and isotopic ([3-(3)H]glucose, [U-(14)C]glucose) techniques were used to assess glucose metabolism. Insulin levels were approximately 40 microU/ml in all groups. Data show that 1) counterregulatory hormone (glucagon, catecholamines, and cortisol) responses to exercise and hypoglycemia combined are synergistically higher than the response to either stimulus alone; 2) exercise-induced increases in insulin action are negated during hypoglycemia by the counterregulatory response; 3) decreased need for exogenous glucose during hypoglycemic compared with euglycemic exercise is due to stimulation of endogenous glucose production, which accounts for approximately 30% of the decrease, and reduction of glucose utilization, which accounts for approximately 70%; and 4) insulin-stimulated nonoxidative glucose metabolism is unaffected by exercise or hypoglycemia, whereas insulin-stimulated oxidative glucose metabolism is selectively increased by exercise and decreased by hypoglycemia. In conclusion, the marked rise in insulin action during exercise is matched, under insulin-induced hypoglycemic conditions, by an equally profound increase in counterregulation. The effectiveness of the potent insulin counterregulatory response may be important in decreasing the magnitude and frequency of exercise-induced hypoglycemia.

scholarly journals NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 120
Author(s):  
Hussein Herz ◽  
Yang Song ◽  
Yuanchao Ye ◽  
Liping Tian ◽  
Benjamin Linden ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Treated Group ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Control Group ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Insulin Levels ◽  
Hepatic Glucose

Background/Aim: Given their widespread use and their notorious effects on the lining of gut cells, including the enteroendocrine cells, we explored if chronic exposure to non-steroidal anti-inflammatory drugs (NSAIDs) affects metabolic balance in a mouse model of NSAID-induced enteropathy. Method: We administered variable NSAIDs to C57Blk/6J mice through intragastric gavage and measured their energy balance, glucose hemostasis, and GLP-1 levels. We treated them with Exendin-9 and Exendin-4 and ran a euglycemic-hyperinsulinemic clamp. Results: Chronic administration of multiple NSAIDs to C57Blk/6J mice induces ileal ulcerations and weight loss in animals consuming a high-fat diet. Despite losing weight, NSAID-treated mice exhibit no improvement in their glucose tolerance. Furthermore, glucose-stimulated (glucagon-like peptide -1) GLP-1 is significantly attenuated in the NSAID-treated groups. In addition, Exendin-9—a GLP-1 receptor antagonist—worsens glucose tolerance in the control group but not in the NSAID-treated group. Finally, the hyper-insulinemic euglycemic clamp study shows that endogenous glucose production, total glucose disposal, and their associated insulin levels were similar among an ibuprofen-treated group and its control. Exendin-4, a GLP-1 receptor agonist, reduces insulin levels in the ibuprofen group compared to their controls for the same glucose exchange rates. Conclusions: Chronic NSAID use can induce small intestinal ulcerations, which can affect intestinal GLP-1 production, hepatic insulin sensitivity, and consequently, hepatic glucose production.

[LeuB24]insulin is an insulin agonist at the liver in vivo

1983 ◽  
Vol 245 (5) ◽  
pp. E483-E488 ◽  
Author(s):  
D. P. Figlewicz ◽  
J. D. Best ◽  
H. S. Tager ◽  
G. J. Taborsky
Keyword(s):  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Significant Drop ◽  
Molar Ratios ◽  
Glucose Levels ◽  
Arterial Plasma

A mutant insulin isolated from the plasma of a diabetic patient has been reported to antagonize insulin action in vitro and was thought to be [LeuB24]insulin. This study examines the ability of [LeuB24]insulin to antagonize insulin action at the liver in vivo in anesthetized dogs. Antagonism of insulin action was first simulated by decreasing the intraportal insulin infusion 50%. This resulted in a significant increase in both glucose production (Ra) (delta = + 0.30 +/- 0.08 mg X kg-1 X min-1) and the glucose level in arterial plasma (delta = +6.5 +/- 2.8 mg/dl), validating the responsiveness of the preparation to partial insulin antagonism. [LeuB24]insulin was infused intraportally, at molar ratios of 1:1, 1:2, 1:4, and 1:10 (50, 25, 12.5, and 5 ng/min, respectively) with insulin (54 ng/min). Infusion at all but the lowest dose resulted in a significant drop in glucose production (delta = -0.44 +/- 0.07, -0.35 +/- 0.06, and -0.28 +/- 0.08 mg X kg-1 X min-1 for4 analogue infusions of 50, 25, and 12.5 ng/min, respectively) and plasma glucose levels (delta = -7 +/- 3 and -3 +/- 1 mg/dl for analogue infusions of 50 and 25 ng/min, respectively). No change in Rd (glucose disposal) was observed for either insulin withdrawal of [LeuB24]insulin infusion. We conclude that, at the liver in vivo, [LeuB24]insulin does not antagonize insulin action but rather acts as an insulin agonist. Its hepatic effects would not contribute to a diabetic hyperglycemia.

scholarly journals High-intensity infrasound effects on glucose metabolism in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gonçalo Martins Pereira ◽  
Madalena Santos ◽  
Sofia S. Pereira ◽  
Gonçalo Borrecho ◽  
Francisco Tortosa ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Glucose Intolerance ◽  
High Intensity ◽  
Tolerance Test ◽  
Muscular Tissue ◽  
Continuous Exposure ◽  
The Impact ◽  
Femoris Muscle

AbstractRecent focus has been given on the effects of high-intensity infrasound (HII) exposure, and whether it induces changes in pancreatic morphology and glucose metabolism is still unknown. As such, we have studied the impact of HII exposure on glucose tolerance, insulin sensitivity, pancreatic islet morphology, muscle GLUT4 and plasma insulin and corticosterone levels. Normal and glucose intolerant wild-type Wistar rats were randomly divided in two groups: one group not exposed to HII and the other continuously exposed to HII. Animals were sacrificed at three timepoints of exposure (1, 6 or 12 weeks). An intraperitoneal glucose tolerance test was performed, blood samples were collected and the pancreas and the quadriceps femoris muscle were excised. Circulating insulin and corticosterone levels were determined and pancreatic and muscular tissue were routinely processed for histochemistry and immunohistochemistry with an anti-GLUT4 antibody. Animals exposed to HII had higher corticosterone levels than animals not exposed. No differences were found on insulin concerning HII exposure or glucose intolerance. Glucose intolerant animals had pancreatic islet fibrosis and no differences were found in GLUT4 ratio concerning HII exposure. In conclusion, we found that continuous exposure to HII increases stress hormone levels without inducing glucose intolerance in rats.

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