Plasma Glucose Disposal Research Articles

A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals.

We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating carbohydrate oxidation and glycogen use would increase the disposal of an ingested glucose load [i.e., oral glucose tolerance test (OGTT); 75 g of glucose]. Separated by at least 1 wk, nine young healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58 ± 5% V̇o2max either in a thermoneutral (21 ± 1°C; NEUTRAL) or in a hot environment (33 ± 1°C; HEAT) eliciting similar energy expenditure (503 ± 101 kcal). These two trials were compared with a no-exercise trial (NO EXER). Twenty minutes after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149 ± 35 vs. 124 ± 31 µmol·kg-1·min-1, P = 0.010). However, during the following OGTT, glucose Rd was similar in HEAT and NEUTRAL trials (i.e., 25.1 ± 3.6 vs. 25.2 ± 5.3 µmol·kg-1·min-1, P = 0.981). Insulin sensitivity (i.e., ISIndexMATSUDA) only improved in NEUTRAL compared with NO EXER (10.1 ± 4.6 vs. 8.8 ± 3.7 au; P = 0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.NEW & NOTEWORTHY Exercise in the heat increases estimated muscle glycogen use. Reduced muscle glycogen after exercise in the heat could increase insulin-mediated glucose uptake during a subsequent oral glucose tolerance test (OGTT). However, plasma glucose kinetics are not improved during the OGTT in response to a bout of exercise in the heat, and insulin sensitivity worsens. Heat stress activates glucose counterregulatory hormones whose actions may linger during the OGTT, preventing increased glucose uptake.

Dataset for 'Pre-Exercise Breakfast Ingestion versus Extended Overnight Fasting Increases Postprandial Glucose Flux after Exercise in Healthy Men: Pre-exercise feeding and postprandial glucose flux'

The aim of this study was to characterise postprandial glucose flux after exercise in the fed versus overnight fasted-state and to investigate potential underlying mechanisms. In a randomized order, twelve men underwent breakfast-rest (BR; 3 h semi-recumbent), breakfast-exercise (BE; 2 h semi-recumbent before 60-min of cycling (50% peak power output) and overnight fasted-exercise (FE; as per BE omitting breakfast) trials. An oral glucose tolerance test (OGTT) was completed post-exercise (post-rest on BR). Dual stable isotope tracers ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. The results from this study showed that consuming breakfast before exercise increases post-exercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally-ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state.

Intestinal Glucose Absorption Is a Key Determinant of 1-Hour Postload Plasma Glucose Levels in Nondiabetic Subjects.

One-hour postload hyperglycemia, defined as 1-hour plasma glucose (1hPG) ≥ 155 mg/dL during an oral glucose tolerance test (OGTT), has been proposed as an independent predictor of type 2 diabetes. Recent evidence suggests that 1-hour hyperglycemia can be explained by enhanced duodenal glucose absorption, which in turn may increase the rate of appearance of oral glucose in the systemic circulation (RaO). However, the impact of RaO on 1hPG and 1-hour glucose excursions (incremental area under the curve calculated through the first hour after glucose ingestion; glucose iAUC1h) is still unknown. We quantified the relative contribution of postload RaO to 1hPG and glucose iAUC1h with respect to other major glucose homeostatic mechanisms in nondiabetic participants. Model-derived β-cell function, insulin clearance, glucose metabolic fluxes, and peripheral and hepatic insulin sensitivity were measured during a 75-g OGTT by a double tracer method in 23 nondiabetic volunteers. Early insulin secretion, whole-body insulin sensitivity, and plasma glucose disposal were significantly impaired in participants with 1hPG ≥ 155 mg/dL (n = 11), who also showed nominally greater RaO (19%; P = 0.10). In multivariable models, postload RaO showed an independent effect on both 1hPG and glucose iAUC1h (partial r2 = 0.26 and 0.48, respectively; P < 0.003). The relative contribution of RaO to 1hPG (23%) and glucose iAUC1h (30%) was similar to that of early insulin secretion and peripheral insulin sensitivity and greater than that of hepatic insulin sensitivity. Our data highlight the primary role of RaO as a major determinant of 1-hour postprandial glucose excursions in nondiabetic participants.

Preexercise breakfast ingestion versus extended overnight fasting increases postprandial glucose flux after exercise in healthy men.

The aim of this study was to characterize postprandial glucose flux after exercise in the fed versus overnight fasted state and to investigate the potential underlying mechanisms. In a randomized order, twelve men underwent breakfast-rest [(BR) 3 h semirecumbent], breakfast-exercise [(BE) 2 h semirecumbent before 60 min of cycling (50% peak power output)], and overnight fasted exercise [(FE) as per BE omitting breakfast] trials. An oral glucose tolerance test (OGTT) was completed after exercise (after rest on BR). Dual stable isotope tracers ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. Breakfast before exercise increased postexercise plasma glucose disposal rates during the OGTT, from 44 g/120 min in FE {35 to 53 g/120 min [mean (normalized 95% confidence interval)] to 73 g/120 min in BE [55 to 90 g/120 min; P = 0.01]}. This higher plasma glucose disposal rate was, however, offset by increased plasma glucose appearance rates (principally OGTT-derived), resulting in a glycemic response that did not differ between BE and FE ( P = 0.11). Plasma I-FABP concentrations during exercise were 264 pg/ml (196 to 332 pg/ml) lower in BE versus FE ( P = 0.01). Breakfast before exercise increases postexercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state.

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP.

Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial.

BackgroundInsulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations.MethodIn a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30-min) after the oral glucose load.ResultsDuring control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice.ConclusionsA single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis.Trial registrationThe study was registered at clinicaltrials.gov on 30th November 2012 (NCT01746329).Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0094-x) contains supplementary material, which is available to authorized users.

Adipose Tissue Dysfunction in Humans: A Potential Role for the Transmembrane Protein ENPP1

Adipose tissue (AT) helps to regulate body fat partitioning and systemic lipid/glucose metabolism. We have recently reported lipid/glucose metabolism abnormalities and increased liver triglyceride content in an AT-selective transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), the AdiposeENPP1-Tg mouse. The aim of the study was to test the translational hypothesis that AT-ENPP1 overexpression associates with AT dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine levels), increased liver triglyceride deposition, and systemic insulin resistance in humans. A total of 134 young normoglycemic men and women were subjected to body composition studies, hyperinsulinemic-euglycemic clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic resonance spectroscopy. Predetermined measures included AT expression of ENPP1 and other lipid metabolism/inflammation genes, plasma adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride content, and the systemic glucose disposal rate. After statistical adjustment for body fat content, increasing AT-ENPP1 was associated with up-regulation of genes involved in NEFA metabolism and inflammation, increased postabsorptive NEFA levels, decreased plasma adiponectin, increased liver triglyceride content, and systemic insulin resistance in men. In women, there were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated with increasing AT-ENPP1, despite increased expression of lipid metabolism and inflammation genes in AT. Increased AT-ENPP1 is associated with AT dysfunction, increased liver triglyceride deposition, and systemic insulin resistance in young normoglycemic men. These findings are concordant with the AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health complications of AT dysfunction, including type 2 diabetes and cardiovascular disease.

Effects of branched chain amino acids infusion on whole‐body plasma glucose disposal: a pilot study

The physiological importance of the inhibition of muscle glucose uptake simultaneously with the stimulation of muscle protein synthesis, when the plasma concentrations of both glucose and amino acids are elevated, as in the fed state, is not clear. We tested the hypothesis that a branched chain amino acids (BCAA) infusion, known to increase protein accumulation, impairs insulin‐stimulated whole‐body glucose disposal. Two groups of young, healthy males and females (n = 5/group) were studied in the postabsorptive state (3 hours) and during a 3 hour euglycemic, hyperinsulinemic (40 mIU/m‐2/min) clamp. The control group (BAS) was infused with BCAA sufficient to maintain plasma BCAA at the basal concentrations during the clamp, while the other group (HI) received a six hour BCAA infusion (1.66 umol/kg/min) to increase BCAA 4‐fold. Subjects in both groups were insulin sensitive as determined by the HOMA index. Glucose disposal rate during the clamp, as determined by 6,6‐d2 glucose infusion and adjusted to the prevailing plasma insulin concentrations, was lower in the HI group (0.53 umol/kg/min +/− 0.05 vs. 0.93 umol/kg/min +/− 0.11; HI vs. BAS; p=0.005). We conclude that increased concentrations of plasma BCAA decrease whole‐body glucose disposal in healthy humans. This protocol will allow us to study the role of plasma amino acids in modulating glucose uptake in skeletal muscle in humans.

Metabolic fate of plasma glucose during hyperglycemia in impaired glucose tolerance: evidence for further early defects in the pathogenesis of type 2 diabetes

We examined the intracellular metabolic fate of plasma glucose during a hyperglycemic clamp in impaired glucose-tolerant (IGT; n = 21) and normal glucose-tolerant subjects (n = 10) using a combination of [3-(3)H]glucose infusion with measurement of [(3)H]water formation and indirect calorimetry. IGT was associated with approximately 35% reduced first-phase insulin responses, normal second-phase insulin response, and 25-30% reduced insulin sensitivity, resulting in approximately 35% reduced plasma glucose disposal. This was coupled with approximately 55% reduced storage of plasma glucose (P < 0.01) and approximately 15-20% reduced glycolysis of plasma glucose (P < 0.03), accounting for approximately 75 and 25% of the reduction in glucose disposal, respectively. Decreased glucose oxidation accounted for virtually all the decrease in glycolysis. Therefore, nonoxidative glycolysis of plasma glucose in IGT was similar to that in NGT (P > 0.9) and accounted for an increased proportion of systemic glucose disposal (P < 0.05). We conclude that, in IGT, decreased disposal of plasma glucose involves mainly decreased glycogen synthesis and to a lesser extent decreased glycolysis, which is accounted for by decreased glucose oxidation. An increased proportion of plasma glucose hence undergoes nonoxidative glycolysis, representing a novel early abnormality in the pathogenesis of T2DM.

Effect of Hoof Trimming before the Dry Period on Productive Performance in Perinatal Dairy Cows

To investigate the effect of hoof trimming before the dry period, the hooves of 10 cows (trimmed group) were trimmed at 79.6 +/- 8.6 days before parturition and the hooves of 52 cows were left untrimmed (control group). Blood biochemistry and hormone concentrations were investigated for 6 cows from each group. The daily milk yield after parturition in the trimmed group tended to be higher than that of the control group. Between 0 and 30 days after parturition, the levels of non-esterified fatty acids were significantly lower stet, and the plasma glucose and glucose disposal rates were significantly higher in the trimmed group. The plasma cortisol concentration was stable before and after parturition in the trimmed group. Hoof trimming before the dry period appears to reduce stress and maintain the nutritional conditions of perinatal dairy cows.

Effects of Increasing Insulin Secretion on Acute Postexercise Blood Glucose Disposal

Coingestion of protein and/or free amino acids with carbohydrate has been reported to accelerate postexercise muscle glycogen synthesis due to an increase in the insulin response. To determine the extent to which the combined ingestion of carbohydrate and a casein protein hydrolysate with or without additional free leucine can increase insulin levels during postexercise recovery in endurance-trained athletes. To determine how this affects whole-body plasma glucose disposal during postexercise recovery. Fourteen male athletes (age: 24.3 +/- 0.8 yr; VO2max: 62.9 +/- 1.4 mL.kg.min) were subjected to three randomized crossover trials in which they performed 2 h of exercise (55% Wmax). Thereafter, subjects were studied for 3.5 h during which they ingested carbohydrate (CHO: 0.8 g.kg.h), carbohydrate and a protein hydrolysate (CHO-PRO: 0.8 and 0.4 g.kg.h, respectively), or carbohydrate, a protein hydrolysate, and free leucine (CHO-PRO-LEU: 0.8, 0.4, and 0.1 g.kg.h, respectively) in a double-blind fashion. Continuous infusions with [6,6-H2] glucose were applied to quantify plasma glucose appearance (Ra) and disappearance rates (Rd). Plasma insulin responses were 108 +/- 17 and 190 +/- 33% greater in the CHO-PRO and CHO-PRO-LEU trial, respectively, compared with the CHO-trial (P < 0.01). Plasma glucose responses were lower in the CHO-PRO and CHO-PRO-LEU trial compared with the CHO-trial (35 +/- 5 and 42 +/- 11% lower, respectively; P < 0.01). Plasma glucose Ra and Rd were greater in the CHO versus the CHO-PRO and CHO-PRO-LEU trials (P < 0.05). Glucose Rd represented 100 +/- 0.03% of Ra in all trials. The combined ingestion of a protein hydrolysate and/or free leucine with carbohydrate (0.8 g.kg.h) substantially augments insulin secretion, but does not affect plasma glucose disposal during the first 3.5 h of postexercise recovery in trained athletes.

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05). This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.

Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes

Although insulin secretion after carbohydrate ingestion is severely impaired in patients with type 2 diabetes, amino acid and protein co-ingestion can substantially increase plasma insulin responses. We investigated insulin responses and the subsequent plasma glucose disposal rates after the ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes. Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1) with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6-(2)H(2)]glucose were then given to investigate plasma glucose disposal. Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The subsequent plasma glucose responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The reduced plasma glucose response in the diabetic patients was attributed to a 13 +/- 3% increase in glucose disposal (P < 0.01). The combined ingestion of carbohydrate with a protein hydrolysate and amino acid mixture significantly increases de novo insulin production in patients with a long-term diagnosis of type 2 diabetes. The increased insulin response stimulates plasma glucose disposal and reduces postprandial glucose concentrations.

Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes

Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes

Inhibition Of Adipose Tissue Lipolysis Increases Intramuscular Lipid Use In Type 2 Diabetes Patients

Numerous studies have reported the association between elevated plasma free fatty acid (FFA) concentrations, intramyocellular triacylglycerol (IMTG) accumulation and the development of insulin resistance. Excess IMTG accretion is the result of an imbalance between FFA uptake, IMTG deposition and its subsequent mobilisation and/or oxidation. Recent data indicate that this imbalance, and not the actual size or distribution of the IMTG pool, is responsible for the development of insulin resistance. Therefore, the turnover of the IMTG pool should form a major therapeutic target in the prevention and treatment of skeletal muscle insulin resistance. PURPOSE To investigate the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use. METHODS Ten type 2 diabetes patients were studied at rest, during exercise and subsequent recovery under normal, fasting conditions (CON) and following administration of a nicotinic acid analogue (LFA). Continuous [U-13C]palmitate and [6,6-2H2]glucose infusions were applied to quantify plasma FFA and glucose oxidation rates, and to estimate intramyocellular lipid and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in fibre type specific lipid and glycogen content. RESULTS In the LFA trial, plasma FFA rate of appearance was effectively reduced, resulting in 2–5 fold lower plasma FFA concentrations (P<0.001). Plasma FFA oxidation rates were substantially reduced at rest, during exercise and recovery in the LFA trial, which was compensated by an increase in both IMTG and endogenous carbohydrate use. Plasma glucose disposal rates did not differ between trials. During exercise, IMTG use averaged 0.18 ± 0.05 vs 0.08 ± 0.03 g/min in the LFA and CON trial, respectively (P<0.01). In accordance to these tracer data, a greater net decline in type I and type II muscle fiber lipid content was observed following exercise in the LFA vs the CON trial (P<0.05). CONCLUSION This study shows that plasma FFA availability regulates IMTG use and introduces adipose tissue lipolytic inhibition as a means to augment IMTG use in type 2 diabetes patients. The latter seems to represent an effective strategy to improve whole-body insulin sensitivity.

Inhibition Of Adipose Tissue Lipolysis Increases Intramuscular Lipid Use In Type 2 Diabetes Patients

Numerous studies have reported the association between elevated plasma free fatty acid (FFA) concentrations, intramyocellular triacylglycerol (IMTG) accumulation and the development of insulin resistance. Excess IMTG accretion is the result of an imbalance between FFA uptake, IMTG deposition and its subsequent mobilisation and/or oxidation. Recent data indicate that this imbalance, and not the actual size or distribution of the IMTG pool, is responsible for the development of insulin resistance. Therefore, the turnover of the IMTG pool should form a major therapeutic target in the prevention and treatment of skeletal muscle insulin resistance. PURPOSE To investigate the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use. METHODS Ten type 2 diabetes patients were studied at rest, during exercise and subsequent recovery under normal, fasting conditions (CON) and following administration of a nicotinic acid analogue (LFA). Continuous [U-13C]palmitate and [6,6-2H2]glucose infusions were applied to quantify plasma FFA and glucose oxidation rates, and to estimate intramyocellular lipid and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in fibre type specific lipid and glycogen content. RESULTS In the LFA trial, plasma FFA rate of appearance was effectively reduced, resulting in 2–5 fold lower plasma FFA concentrations (P<0.001). Plasma FFA oxidation rates were substantially reduced at rest, during exercise and recovery in the LFA trial, which was compensated by an increase in both IMTG and endogenous carbohydrate use. Plasma glucose disposal rates did not differ between trials. During exercise, IMTG use averaged 0.18 ± 0.05 vs 0.08 ± 0.03 g/min in the LFA and CON trial, respectively (P<0.01). In accordance to these tracer data, a greater net decline in type I and type II muscle fiber lipid content was observed following exercise in the LFA vs the CON trial (P<0.05). CONCLUSION This study shows that plasma FFA availability regulates IMTG use and introduces adipose tissue lipolytic inhibition as a means to augment IMTG use in type 2 diabetes patients. The latter seems to represent an effective strategy to improve whole-body insulin sensitivity.

IGF-1 levels, GH peak after GHRH+Arginine and 24h-GH-profile in males with the metabolic syndrome

Abdominal obesity and insulin resistance are central findings in the metabolic syndrome. The metabolic syndrome leads to similar symptoms of growth hormone deficiency (GHD), such as increased body fat mass and decreased lean body mass, disorders of glucose and lipid metabolism. The aim of the present study was to evaluate parameters of GH/IGF-1 axis in patients with the metabolic syndrome and its correlation with characteristic parameters of the metabolic syndrome, such as BMI, waist circumference, abdominal fat mass, fasting plasma glucose (FPG) and glucose disposal rate (GDR). The study group consisted of 25 males with the metabolic syndrome (age 55±5 yr, BMI 33.4±2.8kg/m2, FPG 121±24mg/dL; mean±S.D.). The mean IGF-1 level was 140+47µg/L and GH peaks after GHRH plus arginine (GHRH/ARG) ranged from 1.2 to 15.9µg/L (6.1±3.5µg/L) and were below 5µg/L in 10 males. 24h-GH-secretion correlated with IGF-1 levels (p=<0.0001, r2=0.6). 22/25 (88%) showed a GH response <9µg/L. IGF-1 (p=0.003, r2=0.34) and the mean 24h-GH-secretion (p=0.01, r2=0.32) correlated with the GH peak after GHRH/ARG. The BMI correlated with GH peak after GHRH/ARG (p=0.01, r2=0.21), with the mean 24h-GH-secretion (p=0.02, r2=0.24) and with the IGF-1 levels (p=0.001, r2=0.27). Furthermore, waist circumference correlated with GH peak after GHRH/ARG (p=0.01, r2=0.21), with the mean 24h-GH-secretion (p=0.02, r2=0.25) and with the IGF-1 (p=0.02, r2=0.21). We have seen a trend of correlation between IGF-1 and the abdominal fat mass (p=0.059, r2=0.15). Moreover, we have seen a weak but not significant correlation between GDR and GH peak after GHRH/ARG (p=0.06, r2=0.54). The mean 24h-cortisol-secretion was 224±54 nmol/l and did not correlate with the GH peak after GHRH/ARG (p=0.54, r2=0.1). In conclusion, GH/IGF-1 axis is blunted in patients with the metabolic syndrome. BMI and waist circumference are strong parameters correlating with a diminished somatotropic function. Obesity decreases GH secretion and consequently shares many symptoms of untreated GHD.

Regulation of fuel metabolism by preexercise muscle glycogen content and exercise intensity.

To date, the results of studies that have examined the effects of altering preexercise muscle glycogen content and exercise intensity on endogenous carbohydrate oxidation are equivocal. Differences in the training status of subjects between investigations may, in part, explain these inconsistent findings. Accordingly, we determined the relative effects of exercise intensity and carbohydrate availability on patterns of fuel utilization in the same subjects who performed a random order of four 60-min rides, two at 45% and two at 70% of peak O(2) uptake (Vo(2 peak)), after exercise-diet intervention to manipulate muscle glycogen content. Preexercise muscle glycogen content was 596 +/- 43 and 202 +/- 21 mmol/kg dry mass (P < 0.001) for high-glycogen (HG) and low-glycogen (LG) conditions, respectively. Respiratory exchange ratio was higher for HG than LG during exercise at both 45% (0.85 +/- 0.01 vs. 0.74 +/- 0.01; P < 0.001) and 70% (0.90 +/- 0.01 vs. 0.79 +/- 0.01; P < 0.001) of Vo(2 peak). The contribution of whole body muscle glycogen oxidation to energy expenditure differed between LG and HG for exercise at both 45% (5 +/- 2 vs. 45 +/- 5%; P < 0.001) and 70% (25 +/- 3 vs. 60 +/- 3%; P < 0.001) of Vo(2 peak). Yet, despite marked differences in preexercise muscle glycogen content and its subsequent utilization, rates of plasma glucose disappearance were similar under all conditions. We conclude that, in moderately trained individuals, muscle glycogen availability (low vs. high) does not influence rates of plasma glucose disposal during either low- or moderate-intensity exercise.

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

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&lt;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&lt;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.

Intracellular partition of plasma glucose disposal in hypertensive and normotensive subjects with type 2 diabetes mellitus.

The aim of this study was to ascertain whether the presence of hypertension conveys a more severe degree of insulin resistance in type 2 diabetes mellitus and, if so, which biochemical pathways are involved. We quantitated the rates of total glucose disposal, glycogen synthesis (GS), glycolysis, glucose oxidation, endogenous glucose production, and LOX in the basal state and during a 4-h euglycemic ( approximately 5 mM) hyperinsulinemic ( approximately 300 pM) clamp carried out in combination with a dual-tracer infusion ([(3)H]-3- and [(14)C]-U-D-glucose) and indirect calorimetry in 42 nonobese noninsulin-treated type 2 diabetic subjects (22 hypertensive and 20 normotensive) and 23 nonobese nondiabetic subjects (9 without and 14 with essential hypertension). Compared with normotensive controls, both groups of diabetic subjects were markedly insulin resistant. In the basal state, all glucose fluxes were similar in diabetic subjects with or without hypertension. During insulin infusion, total glucose disposal was significantly reduced in hypertensive diabetic subjects, compared with their normotensive counterparts (18.7 +/- 1.0 vs. 28.6 +/- 3.0 micromol/min.kg lean body mass; P < 0.01). This difference was almost entirely explained by a marked reduction in GS (4.5 +/- 2.0 vs. 12.5 +/- 3.3 micromol/min.kg lean body mass; P < 0.01). Endogenous glucose production was not different in the two diabetic groups during insulin infusion and was significantly higher than in normotensive controls. Lipid oxidation was less suppressed by hyperinsulinemia in hypertensive than in normotensive diabetic subjects (1.46 +/- 0.1 vs. 0.91 +/- 0.1 micromol/min.kg lean body mass; P < 0.01). Glucose fluxes were not significantly different in nondiabetic subjects with essential hypertension and in normotensive diabetic individuals. These results indicate that hypertension markedly aggravates insulin resistance featuring type 2 diabetes mellitus. The molecular defects underlying this phenomenon involve primarily GS.