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.

Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow

2000 ◽  
Vol 279 (6) ◽  
pp. E1264-E1270 ◽  
Author(s):  
Kieren Mather ◽  
Markku Laakso ◽  
Steven Edelman ◽  
Ginger Hook ◽  
Alain Baron
Keyword(s):  
Blood Flow ◽  
Glucose Metabolism ◽  
Whole Body ◽  
Glucose Disposal ◽  
Insulin Stimulation ◽  
Insulin Resistant ◽  
Type 2 Dm ◽  
Glucose Disposal Rate ◽  
Type 2 Diabetic

We hypothesized that the vasodilation observed during insulin stimulation is closely coupled to the rate of glucose metabolism. Lean (L, n = 13), obese nondiabetic (OB, n = 13), and obese type 2 diabetic subjects (Type 2 DM, n = 16) were studied. Leg blood flow (LBF) was examined under conditions of euglycemic hyperinsulinemia (EH) and hyperglycemic hyperinsulinemia (HH), which produced a steady-state whole body glucose disposal rate (GDR) of ∼2,000 μmol · m−2 · min−1. At this GDR, under both conditions, subjects across the range of insulin sensitivity exhibited equivalent LBF (l/min EH: L, 0.42 ± 0.03; OB, 0.43 ± 0.03; Type 2 DM, 0.38 ± 0.07; P= 0.72 by ANOVA. HH: L, 0.44 ± 0.04; OB, 0.39 ± 0.05; Type 2 DM, 0.41 ± 0.04; P = 0.71). The continuous relationship between LBF and GDR did not differ across subject groups [slope × 10−5l/(μmol · m−2 · min−1) by ANOVA. EH: L, 8.6; OB, 9.2; Type 2 DM, 7.9; P = 0.91. HH: L, 4.2; OB, 2.5; Type 2 DM, 4.1; P = 0.77], although this relationship did differ between the EH and HH conditions ( P = 0.001). These findings support a physiological coupling of LBF and insulin-mediated glucose metabolism. The mechanism(s) linking substrate delivery and metabolism appears to be intact in insulin-resistant states.

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.

Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation

2012 ◽  
Vol 303 (12) ◽  
pp. E1397-E1407 ◽  
Author(s):  
Maarten R. Soeters ◽  
Peter B. Soeters ◽  
Marieke G. Schooneman ◽  
Sander M. Houten ◽  
Johannes A. Romijn
Keyword(s):  
Glucose Metabolism ◽  
Glucose Oxidation ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Energy Deficit ◽  
Human Organism ◽  
Starvation Response ◽  
Protein Mass ◽  
Carbon Chains

The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs. From an evolutionary perspective, this lipid-induced effect on glucose oxidation and uptake is very strong and may therefore help to understand why insulin resistance in obesity and type 2 diabetes mellitus is difficult to treat. The importance of reciprocity in lipid and glucose metabolism during human starvation should be taken into account when studying lipid and glucose metabolism in general and in pathophysiological conditions in particular.

scholarly journals Higher Endogenous Glucose Production During OGTT vs Isoglycemic Intravenous Glucose Infusion

2016 ◽  
Vol 101 (11) ◽  
pp. 4377-4384 ◽  
Author(s):  
Asger Lund ◽  
Jonatan I. Bagger ◽  
Mikkel Christensen ◽  
Magnus Grøndahl ◽  
Gerrit van Hall ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Hemoglobin A1c ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Oral Glucose ◽  
Control Subjects ◽  
Nondiabetic Control ◽  
Endogenous Glucose

Context: Oral glucose ingestion elicits a larger insulin response and delayed suppression of glucagon compared to isoglycemic IV glucose infusion (IIGI). Objective: We studied whether these differences translate into effects on endogenous glucose production (EGP) and glucose disposal in patients with type 2 diabetes and nondiabetic control subjects. Design: This was a single-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Ten patients with type 2 diabetes (age, [mean ± SD] 57.1 ± 6.7 years; body mass index, 29.0 ± 4.3 kg/m2; hemoglobin A1c, 53.8 ± 11.0 mmol/mol; duration of diabetes, 9.2 ± 5.0 years) and 10 matched nondiabetic control subjects (age, 56.0±10.7 years; body mass index, 29.8 ± 2.9 kg/m2; hemoglobin A1c, 33.8 ± 5.5 mmol/mol) participated. Interventions: Three experimental days: 75 g-oral glucose tolerance test (OGTT), IIGI, and IIGI+glucagon (IIGI with a concomitant IV glucagon infusion [0.8 ng/kg/min from 0 to 25 minutes] designed to mimic portal glucagon concentrations during OGTT in the type 2 diabetic group) were undertaken. Main Outcome Measures: Glucose kinetics were assessed by tracer methodology. Results: Glucose rate of disappearance was higher during the OGTT vs IIGI in the control group, but similar on all days in the diabetic group. Surprisingly, in both groups, EGP was more suppressed during IIGI than during OGTT, and exogenous glucagon infusion during IIGI did not restore EGP to the levels observed during OGTT. Conclusion: EGP was less suppressed during OGTT than during IIGI in both patients with type 2 diabetes and in nondiabetic control subjects. Based on the present experimental design, it was not possible to attribute this difference to the delayed glucagon suppression observed in the initial phase of the OGTT.

scholarly journals Glucose-mediated glucose disposal in insulin-resistant normoglycemic relatives of type 2 diabetic patients.

Diabetes ◽  
2000 ◽  
Vol 49 (7) ◽  
pp. 1209-1218 ◽  
Author(s):  
J E Henriksen ◽  
K Levin ◽  
P Thye-Rønn ◽  
F Alford ◽  
O Hother-Nielsen ◽  
...  
Keyword(s):  
Glucose Disposal ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

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.

GLP-1 treatment reduces endogenous insulin resistance via activation of central GLP-1 receptors in mice fed a high-fat diet

2010 ◽  
Vol 299 (2) ◽  
pp. E318-E324 ◽  
Author(s):  
Edwin T. Parlevliet ◽  
Judith E. de Leeuw van Weenen ◽  
Johannes A. Romijn ◽  
Hanno Pijl
Keyword(s):  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
High Fat ◽  
Insulin Resistant ◽  
Endogenous Insulin ◽  
Endogenous Glucose ◽  
Glucagon Like Peptide 1 ◽  
The Impact

Glucagon-like peptide-1 (GLP-1) improves insulin sensitivity in humans and rodents. It is currently unknown to what extent the (metabolic) effects of GLP-1 treatment are mediated by central GLP-1 receptors. We studied the impact of central GLP-1 receptor (GLP-1R) antagonism on the metabolic effects of peripheral GLP-1 administration in mice. High-fat-fed insulin-resistant C57Bl/6 mice were treated with continuous subcutaneous infusion of GLP-1 or saline (PBS) for 2 wk, whereas the GLP-1R antagonist exendin-9 (EX-9) and cerebrospinal fluid (CSF) were simultaneously infused in the left lateral cerebral ventricle (icv). Glucose and glycerol turnover were determined during a hyperinsulinemic euglycemic clamp. VLDL-triglyceride (VLDL-TG) production was determined in hyperinsulinemic conditions. Our data show that the rate of glucose infusion necessary to maintain euglycemia was significantly increased by GLP-1. Simultaneous icv infusion of EX-9 diminished this effect by 62%. The capacities of insulin to stimulate glucose disposal and inhibit glucose production were reinforced by GLP-1. Simultaneous icv infusion of EX-9 significantly diminished the latter effect. Central GLP-1R antagonism alone did not affect glucose metabolism. Also, GLP-1 treatment reinforced the inhibitory action of insulin on VLDL-TG production. In conclusion, peripheral administration of GLP-1 reinforces the ability of insulin to suppress endogenous glucose and VLDL-TG production (but not lipolysis) and boosts its capacity to stimulate glucose disposal in high-fat-fed C57Bl/6 mice. Activation of central GLP-1Rs contributes substantially to the inhibition of endogenous glucose production by GLP-1 treatment in this animal model.

scholarly journals Pathophysiology and Pharmacological Treatment of Insulin Resistance*

2000 ◽  
Vol 21 (6) ◽  
pp. 585-618 ◽  
Author(s):  
Stephan Matthaei ◽  
Michael Stumvoll ◽  
Monika Kellerer ◽  
Hans-Ulrich Häring
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Progressive Disease ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Pharmacological Agents ◽  
Cell Dysfunction ◽  
Glucosidase Inhibitors ◽  
Type 2 Diabetic

Abstract Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic β-cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., α-glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease.

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