scholarly journals Quantitative kinetics of glucose appearance and disposal following a13C-labelled starch-rich meal: comparison of male and female subjects

2002 ◽  
Vol 87 (6) ◽  
pp. 569-577 ◽  
Author(s):  
M. Denise Robertson ◽  
Geoff Livesey ◽  
John C. Mathers
Keyword(s):  
Insulin Sensitivity ◽  
Indirect Calorimetry ◽  
Compartment Model ◽  
Whole Body ◽  
Glucose Disposal ◽  
Female Group ◽  
Acute Response ◽  
Fractional Rate ◽  
Steady State Kinetics ◽  
The Uk

In the UK, starch contributes up to 25 % of energy intake in adults (). The present study investigated the acute response to a starchy meal on whole-body glucose metabolism and assessed insulin sensitivity in men compared with women. Low insulin sensitivity has been postulated to pre-dispose individuals to a cluster of associated abnormalities known to increase the risk of CHD. Metabolic responses to a13C-labelled meal were determined in conjunction with a primed continuous infusion of D-[6,6-2H]glucose in groups of healthy age- and BMI-matched men and women. Peripheral plasma glucose disposal (Gd) was computed using non-steady state kinetics in a single compartment model, simultaneously with determination of whole-body net glucose oxidation by indirect calorimetry. Insulin sensitivity was derived using cumulative Gd as the dependent variable, and time and the integrated insulin concentration as independent variables. The female group had the higher fractional rate of glucose appearance in plasma from starch (P=0·019) immediately after ingestion. Females also had a higher rate of plasma Gd and a significantly higher insulin-dependent Gd (6·8v.5·6 μg glucose/(min.kg) per pmol insulin,P<0·05) compared with the males. A smaller absolute pool of endogenous glucose in females allowed the rate of exogenous13CO2production to be significantly higher in the females (P=0·007) corresponding also to a significantly higher (P<0·05) carbohydrate oxidation rate obtained by indirect calorimetry. The present study suggests that during the ingestion of a starchy meal, females exhibit higher glucose flux and greater whole-body insulin sensitivity than males.

scholarly journals Evidence for altered control of glucose disposal after total colectomy

2000 ◽  
Vol 84 (6) ◽  
pp. 813-819 ◽  
Author(s):  
M. Denise Robertson ◽  
Geoff Livesey ◽  
Shelagh M. Hampton ◽  
John C. Mathers
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Resistance Syndrome ◽  
Compartment Model ◽  
Short Chain Fatty Acids ◽  
Postprandial Glucose ◽  
Insulin Concentration ◽  
Glucose Disposal ◽  
Control Group ◽  
Plasma Insulin Concentration ◽  
Steady State Kinetics

Colonic fermentation of organic matter to short-chain fatty acids has been implicated in the improvement in insulin sensitivity achieved by feeding diets rich in complex carbohydrates. The present study assessed the potential role of the colon in determining postprandial glucose kinetics. Metabolic responses to a complex-carbohydrate test meal were determined in conjunction with a primed continuous infusion of D-[6,6-2H]glucose in a group of ileostomists and sex-matched controls. Glucose disposal (GD) was computed using non-steady-state kinetics on a single compartment model. Insulin sensitivity was derived using cumulative GD as the dependent variable, and time and the integrated insulin concentration as independent variables. The ileostomist group had a significantly higher postprandial plasma insulin concentration (P=0·034) compared with the control group, but no difference in the plasma glucose concentration. Total GD was similar in each group, although the insulin-dependent GD was substantially lower in the ileostomists (0·46 v. 0·13 mg glucose/min per pmol, P=0·015). The ileostomist group also showed a 50 % lower rate of glucose oxidation in the postprandial period (P=0·005), although the rate of non-oxidative GD was not significantly affected. The present study indicates that loss of the colon is associated with several characteristics of the insulin resistance syndrome, and favours a view that the colon has a role in the control of postprandial glucose.

Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats

1994 ◽  
Vol 77 (2) ◽  
pp. 534-541 ◽  
Author(s):  
J. Gao ◽  
W. M. Sherman ◽  
S. A. McCune ◽  
K. Osei
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Insulin Responsiveness ◽  
Obese Male

This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin-dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic-hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc-facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not “normalize” the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat.

Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance

2013 ◽  
Vol 38 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Steven K. Malin ◽  
Barry Braun
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Oxygen Uptake ◽  
Indirect Calorimetry ◽  
Substrate Utilization ◽  
Peak Oxygen Uptake ◽  
Whole Body ◽  
Glucose Kinetics

Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p < 0.05), with no differences between groups. Blood glucose use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

scholarly journals Loss of PDGF-B activity increases hepatic vascular permeability and enhances insulin sensitivity

2011 ◽  
Vol 301 (3) ◽  
pp. E517-E526 ◽  
Author(s):  
Summer M. Raines ◽  
Oliver C. Richards ◽  
Lindsay R. Schneider ◽  
Kathryn L. Schueler ◽  
Mary E. Rabaglia ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Basolateral Membrane ◽  
Tolerance Test ◽  
Whole Body ◽  
Glucose Disposal ◽  
Permeability Barrier ◽  
Loss Of Function ◽  
Transendothelial Transport

Hepatic vasculature is not thought to pose a permeability barrier for diffusion of macromolecules from the bloodstream to hepatocytes. In contrast, in extrahepatic tissues, the microvasculature is critically important for insulin action, because transport of insulin across the endothelial cell layer is rate limiting for insulin-stimulated glucose disposal. However, very little is known concerning the role in this process of pericytes, the mural cells lining the basolateral membrane of endothelial cells. PDGF-B is a growth factor involved in the recruitment and function of pericytes. We studied insulin action in mice expressing PDGF-B lacking the proteoglycan binding domain, producing a protein with a partial loss of function (PDGF-B ret/ ret). Insulin action was assessed through measurements of insulin signaling and insulin and glucose tolerance tests. PDGF-B deficiency enhanced hepatic vascular transendothelial transport. One outcome of this change was an increase in hepatic insulin signaling. This correlated with enhanced whole body glucose homeostasis and increased insulin clearance from the circulation during an insulin tolerance test. In obese mice, PDGF-B deficiency was associated with an 80% reduction in fasting insulin and drastically reduced insulin secretion. These mice did not have significantly higher glucose levels, reflecting a dramatic increase in insulin action. Our findings show that, despite already having a high permeability, hepatic transendothelial transport can be further enhanced. To the best of our knowledge, this is the first study to connect PDGF-B-induced changes in hepatic sinusoidal transport to changes in insulin action, demonstrating a link between PDGF-B signaling and insulin sensitivity.

scholarly journals Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians

2001 ◽  
Vol 86 (4) ◽  
pp. 515-519 ◽  
Author(s):  
Nancy W. Hua ◽  
Riccardo A. Stoohs ◽  
Francesco S. Facchini
Keyword(s):  
Steady State ◽  
Insulin Sensitivity ◽  
Animal Studies ◽  
Iron Status ◽  
Whole Body ◽  
Glucose Disposal ◽  
Lower Body ◽  
Ferritin Concentration ◽  
Serum Ferritin Concentration ◽  
Glucose Tolerant

The efficacy of insulin in stimulating whole-body glucose disposal (insulin sensitivity) was quantified using direct methodology in thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4·1 (95 % CI 3·5, 5·0)v.6·9 (95 % CI 5·2, 7·5; P=0·0028) respectively. In addition, lacto-ovo vegetarians had lower body Fe stores, as indicated by a serum ferritin concentration (μg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45, 100) for meat-eaters (P=0·0012). To test whether or not Fe status might modulate insulin sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels similar to that seen in vegetarians, with a resultant approximately 40 % enhancement of insulin-mediated glucose disposal (P=0·0008). Our results demonstrate that lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than meat-eaters. In addition, it seems that reduced insulin sensitivity in meat-eaters is amenable to improvement by reducing body Fe. The latter finding is in agreement with results from animal studies where, no matter how induced, Fe depletion consistently enhanced glucose disposal.

scholarly journals Small intestinal metabolism is central to whole-body insulin resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322073
Author(s):  
Giulia Angelini ◽  
Serenella Salinari ◽  
Lidia Castagneto-Gissey ◽  
Alessandro Bertuzzi ◽  
James Casella-Mariolo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Insulin Signalling ◽  
Whole Body ◽  
Glucose Disposal ◽  
Jejunal Loop ◽  
Oral Glucose ◽  
Metabolic Signature ◽  
Jejunal Bypass

ObjectiveTo assess the role of jejunum in insulin resistance in humans and in experimental animals.DesignTwenty-four subjects undergoing biliopancreatic diversion (BPD) or Roux-en-Y gastric bypass (RYGB) were enrolled. Insulin sensitivity was measured at baseline and at 1 week after surgery using oral glucose minimal model.We excluded the jejunum from intestinal continuity in pigs and created a jejunal loop with its vascular and nerve supply intact accessible from two cutaneous stomas, and reconnected the bowel with an end-to-end anastomosis. Glucose stable isotopes were given in the stomach or in the jejunal loop.In vitro studies using primary porcine and human hepatocytes or myoblasts tested the effects of plasma on gluconeogenesis or glucose uptake and insulin signalling.ResultsWhole-body insulin sensitivity (SI∙104: 0.54±0.12 before vs 0.82±0.11 after BPD, p=0.024 and 0.41±0.09 before vs 0.65±0.09/pM/min after RYGB, p=not significant) and Glucose Disposition Index increased only after BPD. In pigs, insulin sensitivity was significantly lower when glucose was administered in the jejunal loop than in the stomach (glucose rate of disappearance (Rd) area under the curve (AUC)/insulin AUC∙10: 1.82±0.31 vs 2.96±0.33 mmol/pM/min, p=0.0017).Metabolomics showed a similar pattern before surgery and during jejunal-loop stimulation, pointing to a higher expression of gluconeogenetic substrates, a metabolic signature of impaired insulin sensitivity.A greater hepatocyte phosphoenolpyruvate-carboxykinase and glucose-6-phosphatase gene expression was elicited with plasma from porcine jejunal loop or before surgery compared with plasma from jejunectomy in pigs or jejunal bypass in humans.Stimulation of myoblasts with plasma from porcine jejunal loop or before surgery reduced glucose uptake, Ser473-Akt phosphorylation and GLUT4 expression compared with plasma obtained during gastric glucose administration after jejunectomy in pigs or after jejunal bypass in humans.ConclusionProximal gut plays a crucial role in controlling insulin sensitivity through a distinctive metabolic signature involving hepatic gluconeogenesis and muscle insulin resistance. Bypassing the jejunum is beneficial in terms of insulin-mediated glucose disposal in obesity.Trial registration numberNCT03111953.

Specific adaptations in muscle and adipose tissue in response to chronic systemic glucose oversupply in rats

1997 ◽  
Vol 273 (1) ◽  
pp. E1-E9 ◽  
Author(s):  
D. R. Laybutt ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Infusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Saline Control ◽  
Slow Increase ◽  
Glucose Clearance

Rats minimize hyperglycemia during chronic glucose infusion, but the metabolic processes are unclear. We investigated the tissues involved and the role of altered insulin sensitivity. Cannulated rats were infused with glucose (40 mg.kg-1.min-1) for 1 or 4 days or with saline (control). Hyperglycemia at 1 day (15.3 +/- 1.0 mM) was absent at 4 days (7.5 +/- 0.3 mM), but hyperinsulinemia persisted. Whole body glucose disposal was similarly elevated at 1 and 4 days, implying increased glucose clearance at 4 days (2-fold, P < 0.001). Muscle glucose uptake and glycogen content declined in glucose-infused rats from 1 to 4 days, whereas white adipose tissue (WAT) glucose uptake (6-fold, P < 0.001) and lipogenesis (3-fold, P < 0.001) increased. Muscle and liver triglyceride were doubled at both 1 and 4 days (P < 0.05 vs. control). Insulin sensitivity (assessed during euglycemic clamps) decreased in muscle to 34% of control at 1 and 4 days (P < 0.001 vs. control) and increased fivefold in WAT from 1 to 4 days (P < 0.05). Thus chronic glucose infusion results in a slow increase in efficiency of glucose clearance with enhanced WAT glucose uptake, lipogenesis, and insulin action. In contrast, the adaptation reduces glucose oversupply to muscle. Muscle shows sustained insulin resistance, with lipid accumulation a possible contributing factor.

Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery

1998 ◽  
Vol 275 (1) ◽  
pp. E140-E148 ◽  
Author(s):  
Jonas O. Nygren ◽  
Anders Thorell ◽  
Mattias Soop ◽  
Suad Efendic ◽  
Kerstin Brismar ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Metabolic Response ◽  
Elective Surgery ◽  
Substrate Utilization ◽  
Glucose Infusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Insulin Group ◽  
Postoperative Changes

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (d-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (−40 and −29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.

Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats

1985 ◽  
Vol 248 (5) ◽  
pp. E567-E574 ◽  
Author(s):  
D. E. James ◽  
A. B. Jenkins ◽  
E. W. Kraegen
Keyword(s):  
Insulin Sensitivity ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Relative Proportion ◽  
Glycogen Storage ◽  
Whole Body ◽  
Glucose Disposal ◽  
Maximal Effect ◽  
Euglycemic Hyperinsulinemic Clamp

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

Effect of exercise training on whole-body insulin sensitivity and responsiveness

1984 ◽  
Vol 56 (5) ◽  
pp. 1217-1222 ◽  
Author(s):  
D. E. James ◽  
E. W. Kraegen ◽  
D. J. Chisholm
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Utilization ◽  
Insulin Receptors ◽  
Whole Body ◽  
Glucose Disposal ◽  
Significant Shift ◽  
Insulin Levels ◽  
Plasma Insulin Levels

Exercise training causes a decline in basal and glucose-stimulated plasma insulin levels and improves glucose tolerance. Furthermore evidence has been presented for effects on both insulin receptors and postreceptor events. However, it is unclear how these changes affect the in vivo dose-response relationship between insulin levels and whole-body glucose utilization. The aim was to examine the effect of exercise training on this relationship and distinguish between changes in insulin sensitivity and responsiveness. Euglycemic clamps were performed in trained (ET, running 1 h/day for 7 wk), sedentary (CON), and sedentary food-restricted ( SFR ) rats. ET rats showed no increase in maximal net glucose utilization in response to insulin (ET 29.5 +/- 0.6 vs. CON 28.2 +/- 1.5 mg X kg-1 X min-1, NS), whereas insulin sensitivity was increased as indicated by the insulin concentration causing half-maximal stimulation (ED50) (49 +/- 20 for ET and 133 +/- 30 mU/l for CON). Thus 7 wk of moderate exercise training resulted in a significant shift of whole-body insulin sensitivity to place ED50 well within the physiological range of insulin concentrations. This would undoubtedly result in improved glucose disposal in the postprandial state and emphasizes the potential benefit of exercise in obesity and type II diabetes.

Sign in / Sign up

Export Citation Format

Share Document