Exercise-induced Improvements In Insulin Sensitivity Research Articles

Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight.

Obesity and insulin resistance may be associated with altered expression and secretion of adipokines. Physical activity can markedly improve insulin sensitivity, but the association with adipokines remains largely unknown. In this study, we examined the effects of physical activity on the subcutaneous white adipose tissue (scWAT) secretome and its relationship to insulin sensitivity. As reported previously, we enrolled 26 sedentary, middle-aged men (13 dysglycaemic and overweight; 13 normoglycaemic and of healthy weight) into a 12week, supervised, intensive physical exercise intervention that included two endurance and two resistance sessions each week. Insulin sensitivity was measured as the glucose infusion rate from a euglycaemic-hyperinsulinaemic clamp. In our previous study, we measured maximum oxygen uptake, upper- and lower-body strength and a range of circulating biomarkers, and quantified adipose tissue depots using MRI and magnetic resonance spectroscopy. We have now performed global mRNA sequencing, microarrays and RT-PCR of scWAT and skeletal muscle biopsies, and quantified selected plasma adipokines by ELISA. Insulin sensitivity increased similarly in both dysglycaemic (45%) and normoglycaemic (38%) men after 12weeks of exercise, as reported previously. mRNA sequencing of scWAT revealed 90 transcripts that responded to exercise in dysglycaemic men, whereas only marginal changes were observed in normoglycaemic men. These results were validated using microarrays and RT-PCR. A total of 62 out of 90 transcripts encoded secreted proteins. Overall, 17 transcripts were upregulated and 73 transcripts were downregulated. Downregulated transcripts included several macrophage markers, and were associated with inflammatory and immune-related pathways. Levels of these immune-related transcripts were enhanced in dysglycaemic men vs normoglycaemic men at baseline, but were normalised after the exercise intervention. Principal component and correlation analyses revealed inverse correlations between levels of these immune-related transcripts and insulin sensitivity at baseline, after the intervention, and for the change between baseline and after the intervention. In addition, levels of these transcripts at baseline could predict exercise-induced improvements in insulin sensitivity. Adipokine levels in scWAT (but not in skeletal muscle) were significantly correlated with corresponding plasma adipokine concentrations, as exemplified by leptin, high-molecular-weight adiponectin and secreted frizzled-related protein 4 (SFRP4). SFRP4 mRNA was the most exercise-responsive transcript in scWAT from dysglycaemic men, and plasma SFRP4 concentrations were reduced in dysglycaemic men, but not in normoglycaemic men, after 12weeks of exercise. This study indicates that scWAT may be an important mediator of exercise-induced improvements in insulin sensitivity, especially in overweight dysglycaemic individuals at increased risk of developing type 2 diabetes.

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO2max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.

Family History of Diabetes Does Not Affect Exercise-Induced Improvements in Insulin Sensitivity and Metabolic Flexibility

A family history of diabetes (FH+) is considered a risk factor to develop insulin resistance and type 2 diabetes. However, it is not known whether exercise induced improvement in insulin sensitivity (IS) and metabolic flexibility (MF) are impacted by a FH+, compared to those without (FH-). PURPOSE: To determine if a FH+ limits exercise induced improvements in IS, MF, body composition, and strength following an 8-week combined aerobic and resistance training intervention. METHODS: 19 sedentary, normoglycemic, Mexican-American males underwent 8 weeks of combined exercise training 3 times/week (35-min aerobic & 45-min resistance training/session). A controlled diet was provided 5 days before pre/post intervention tests. IS was assessed by hyperinsulinemic euglycemic clamp. MF was assessed by change in respiratory quotient (ΔRQ) at the insulin stimulated state of the clamp compared to the fasted state. Body composition was measured using DXA. Upper/lower body strength were measured by 1 repetition maximum bench press and leg strength dynamometer. RESULTS: IS significantly improved in both groups (FH- 2.95±31 to 3.84±0.31ml/kg estimated mean body size (EMBS), p=0.03; FH+ 3.6±0.5 to 4.8±0.5ml/kg EMBS; p=0.002). MF significantly improved in both groups (FH- 0.72±0.009 to 0.78±0.008, p=0.001; FH+ 0.70±0.01 to 0.80±0.02, p=0.0001). Fat free mass significantly improved in both groups (FH- 56.6±2.1 to 58.5±2.1kg, p=0.01; FH+ 51.8±1.95 to 53.4±1.79kg, p=0.01). Upper body strength (FH- 172.78±20.95 to 200.56±20.74lb, p=0.0001; FH+ 136.5±14.06 to 168.33±15.29lb, p=0.0001) and lower body strength (FH- 368.89±31.02 to 431.11±22.58lb, p=0.007; FH+ 341.0±22.03 to 412.78±16.22lb, p=0.0001) significantly increased in both groups. Degrees of improvement in IS was not different between groups (FH- 28.3±13.6% vs. FH+ 41.66±11.9%; p>0.05). CONCLUSION: FH+ is not a limiting factor for exercise induced improvements in IS, MF, body composition, and strength in normoglycemic Mexican Americans.

Blood Flow Restriction Fails to Alter Adiponectin Response to an Acute Low-Intensity Resistance Exercise Session

Blood flow restriction (BFR) combined with low-intensity resistance training has been shown to improve muscle strength and hypertrophy, providing a potential important training tool for those incapable of completing more intense resistance training. Adiponectin appears to play a role in exercise-induced improvements in insulin sensitivity and inflammatory state, however little is known regarding the effects of BFR and low-intensity resistance training on adiponectin following exercise. PURPOSE: To determine the effects of bilateral BFR on the salivary adiponectin response to a single session of low-intensity leg press exercises. METHODS: Thirteen healthy males and females aged 18-28 yrs completed two low-intensity resistance exercise sessions (control and BFR) in randomized order with 5-7 d between trials following screening and the determination of 1-RM. Blood pressure cuffs were placed in the uppermost potion of each thigh and were inflated just enough to keep them from falling off the legs (control) or to 90 to 100 mm Hg (BFR). The low-intensity resistance exercise session consisted of four sets of leg press (30 reps first set and 15 reps for following three sets) at 30% 1-RM at 30 reps/min with 30 s of rest between each set. Salivary samples were collected from 3-4 h fasted subjects at baseline, immediately after, and 30 min after the end of exercise for the determination adiponectin concentration. RESULTS: Salivary adiponectin concentration did not significantly increase from baseline (4.2 ± 2.0 ng/ml) to post exercise in the control condition (9.4 ± 6.7 and 2.5 ± 0.6 ng/ml, immediately and 30 min post, p > 0.05). While BFR appeared to result in higher salivary adiponectin concentrations after exercise, they did not change significantly from baseline nor were they significantly different from control at corresponding time points (6.9 ± 3.5, 17.4 ± 13.1, and 4.4 ± 2.1 ng/ml, baseline, immediately and 30 min post, p > 0.05). CONCLUSION: Bilateral BFR combined with low-intensity leg press exercise is not sufficient to produce a significant increase in post exercise salivary adiponectin. Future studies should evaluate whether BFR combined with low-intensity resistance exercise sessions with a greater volume of work have the potential of increasing the adiponectin response.

Effect Of Hypertriglyceridemia, Sugar Ingestion, And Exercise On Substrate Metabolism In Overweight And Obese Individuals

Carbohydrate ingestion may induce oxidative stress, inflammation, impaired insulin action, and altered substrate metabolism in a way that may counteract exercise-induced improvements in insulin sensitivity and metabolic flexibility. Benefits from exercise may differ in individuals with hypertriglyceredemia (hyperTG) compared to individuals with normal TG (normTG). HyperTG and sugar ingestion are linked to metabolic disease. PURPOSE: Compare the triglyceride (TG), glucose (Glu), insulin (Ins), and C-peptide (CPEP) responses between exercise bouts with sugar sweetened beverage consumption (EX+SSB) verses water only (EX+H2O). METHODS: Overweight and obese men (n=9) and women (n=11) (18-55 years) with fasting TG > (hyperTG) or < (normTG) 150 mg·dl-1 completed exercise. Each exercise was a 45-minute 10% grade uphill walk at 65% predicted VO2max. A standard, isocaloric diet to meet energy needs was given post exercise in the EX+H2O condition, but SSB replaced 2 g per kg lean mass of calories from food in the EX+SSB condition. An oral glucose tolerance test (OGTT) was completed the next day. Blood samples were collected pre-, 15, 30, 45, 60, 90, and 120-minutes post-OGTT for analysis of TG, Glu, Ins, and CPEP. Respiratory exchange ratio (RER) was measured collecting expired gas. RESULTS: The release of insulin, as measured by CPEP from 0 to 30 min of the OGTT, was lower (p=0.04) while fasting TG were higher (p=0.03) for the EX+SSB condition (mean±SEM; 178.5±22.5 mg·dl-1) compared to the EX+H2O condition (148.4±14.1 mg·dl-1). Glucose area under the curve was higher (p<0.001) in the normTG group compared to the hyperTG group in the EX+H2O condition. Resting RER was lower (p=0.05) in the normTG group (0.74±0.03 VCO2/VO2) compared to the hyperTG group (0.78±0.04 VCO2/VO2) in the EX+H2O condition. CONCLUSION: Consuming sugar with exercise was followed by higher fasting TG and lower Glu and Ins responses compared to EX+H2O during the OGTT. Fat utilization and metabolic flexibility during the OGTT were lower in the hyperTG group compared to the normTG group. Sugar consumption affected post-exercise metabolism more negatively in individuals with hyperTG. Supported by the Mountain West Clinical Translational Research - Infrastructure Network under a grant from NIGMS of the NIH under Award Number 1U54GM104944.

The Effect of Regular Exercise on Insulin Sensitivity in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session.

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation.

Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle.

One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTOR(Ser2448), TSC2(Ser939), p70S6K(Thr412), and RPS6(Ser235/236)) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTOR(Ser2448), TSC2(Ser939), and RPS6(Ser235/236)). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40(Thr246) and p70S6K(Thr412)) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2 years, BMI: 34.2±1.1kg/m2) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/day for 5 days/week at ∼85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m2/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P<0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P<0.001) and decreased HOMA-IR by 15% (P<0.05). Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=−0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=−0.54; P<0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r=−0.64; P<0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome.

Exercise Therapy in Type 2 Diabetes

OBJECTIVEGiven the transient nature of exercise-induced improvements in insulin sensitivity, it has been speculated that daily exercise is preferred to maximize the benefits of exercise for glycemic control. The current study investigates the impact of daily exercise versus exercise performed every other day on glycemic control in type 2 diabetic patients.RESEARCH DESIGN AND METHODSThirty type 2 diabetic patients (age 60 ± 1 years, BMI 30.4 ± 0.7 kg/m2, and HbA1c 7.2 ± 0.2%) participated in a randomized crossover experiment. Subjects were studied on three occasions for 3 days under strict dietary standardization but otherwise free-living conditions. Blood glucose homeostasis was assessed by continuous glucose monitoring over 48 h during which subjects performed no exercise (control) or 60 min of cycling exercise (50% maximal workload capacity) distributed either as a single session performed every other day or as 30 min of exercise performed daily.RESULTSThe prevalence of hyperglycemia (blood glucose >10 mmol/L) was reduced from 7:40 ± 1:00 h:min per day (32 ± 4% of the time) to 5:46 ± 0:58 and 5:51 ± 0:47 h:min per day, representing 24 ± 4 and 24 ± 3% of the time, when exercise was performed either daily or every other day, respectively (P < 0.001 for both treatments). No differences were observed between the impact of daily exercise and exercise performed every other day.CONCLUSIONSA short 30-min session of moderate-intensity endurance-type exercise substantially reduces the prevalence of hyperglycemia throughout the subsequent day in type 2 diabetic patients. When total work is being matched, daily exercise does not further improve daily glycemia compared with exercise performed every other day.

PS7 - 41. Exercise therapy in type 2 diabetes: Is daily exercise required to optimize glycemic control?

Given the transient nature of exercise-induced improvements in insulin sensitivity, exercise guidelines for type 2 diabetes state that aerobic exercise should be performed at least 3 days/week with no more than 2 consecutive days between exercise sessions. It has been speculated, however, that daily exercise would be preferable to maximize the benefits on glycemic control. The present study investigated the impact of daily exercise versus exercise performed every other day on daily glycemic control in type 2 diabetic patients.

PGC-1α-induced improvements in skeletal muscle metabolism and insulin sensitivityThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α), a nuclear encoded transcriptional coactivator, increases the expression of many genes in skeletal muscle, including those involved with fatty acid oxidation and oxidative phosphorylation. Exercise increases the expression of PGC-1α, and the exercise-induced upregulation of many genes is attributable, in part, to the preceding activation and upregulation of PGC-1α. Indeed, PGC-1α overexpression, like exercise training, increases exercise performance. PGC-1α reductions in humans have been observed in type 2 diabetes, while, in cell lines, PGC-1α mimics the exercise-induced improvement in insulin sensitivity. However, unexpectedly, in mammalian muscle, PGC-1α overexpression contributed to the development of diet-induced insulin resistance. This may have been related to the massive overexpression of PGC-1α, which induced the upregulation of the fatty acid transporter FAT/CD36 and led to an increase in intramuscular lipids, which interfere with insulin signalling. In contrast, when PGC-1α was overexpressed modestly, within physiological limits, mitochondrial fatty acid oxidation was increased, GLUT4 expression was upregulated, and insulin-stimulated glucose transport was increased. More recently, similar PGC-1α-induced improvements in the insulin-resistant skeletal muscle of obese Zucker rats have been observed. These studies suggest that massive PGC-1α overexpression, but not physiologic PGC-1α overexpression, induces deleterious metabolic effects, and that exercise-induced improvements in insulin sensitivity are induced, in part, by the exercise-induced upregulation of PGC-1α.

Metabolomics as a tool to evaluate exercise-induced improvements in insulin sensitivity

Exercise affects substrate utilisation and insulin sensitivity, which in turn improve blood glucose and lipid levels in subjects with type 2 diabetes (T2D). However, making long-lasting lifestyle-changes might be more realistic if the results were easier to record. Screening for biomarkers reflecting metabolic fitness could thus serve as a tool for maintained motivation. The aim of this study was to test the possibility that metabolomics can be used to identify individuals with improved insulin sensitivity as a result of increased physical activity. Healthy and diabetic subjects were investigated before and after 3 months of exercise to determine various metabolic parameters. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamps and found to be improved in the diabetic men. Plasma was collected during the clamp and analyzed through GC/TOFMS. Healthy subjects could be distinguished from diabetics by means of low molecular-weight compounds (LMC) in plasma independently of gender or exercise, and exercise induced differences in LMC patterns both for healthy and T2D subjects. Forty-four significant metabolites were found to explain differences between LMC patterns obtained from trained and non-trained diabetics. Among these compounds, 17 could be annotated and 5 classified. Inositol-1-phosphate showed the highest correlation to insulin sensitivity in diabetic men, whereas an as yet unknown fatty acid correlated best with insulin sensitivity in women. Both metabolites were better correlated to insulin sensitivity than glucose. Finally, the finding that inostitol-1-phosphate negatively correlates with insulin sensitivity in diabetic men, was validated using samples obtained from a similar training study on diabetic men.

Effect of Exercise Intensity on Glucose and Insulin Metabolism in Obese Individuals and Obese NIDDM Patients

The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak. It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.