scholarly journals Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes

2010 ◽  
Vol 108 (5) ◽  
pp. 1134-1141 ◽  
Author(s):  
Bryan C. Bergman ◽  
Leigh Perreault ◽  
Devon M. Hunerdosse ◽  
Mary C. Koehler ◽  
Ali M. Samek ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Action ◽  
Lipid Synthesis ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Synthesis Rate ◽  
Dietary Control ◽  
Intravenous Glucose ◽  
Intramuscular Lipid

Intramuscular triglyceride (IMTG) has received considerable attention as a potential mechanism promoting insulin resistance. Endurance-trained athletes have high amounts of IMTG but are insulin sensitive, suggesting IMTG content alone does not change insulin action. Recent data suggest increased muscle lipid synthesis protects against fat-induced insulin resistance. We hypothesized that rates of IMTG synthesis at rest would be increased in athletes compared with controls. Eleven sedentary men and 11 endurance-trained male cyclists participated in this study. An intravenous glucose tolerance test was performed to assess insulin action. After 3 days of dietary control and an overnight fast, [13C16]palmitate was infused at 0.0174 μmol·kg−1·min−1 for 4 h, followed by a muscle biopsy to measure isotope incorporation into IMTG and diacylglycerol. Compared with controls, athletes were twice as insulin sensitive ( P = 0.004) and had a significantly greater resting IMTG concentration (athletes: 20.4 ± 1.6 μg IMTG/mg dry wt, controls: 14.5 ± 1.8 μg IMTG/mg dry wt, P = 0.04) and IMTG fractional synthesis rate (athletes: 1.56 ± 0.37%/h, controls: 0.61 ± 0.15%/h, P = 0.03). Stearoyl-CoA desaturase 1 mRNA expression ( P = 0.02) and protein content ( P = 0.03) were also significantly greater in athletes. Diacylglycerol, but not IMTG, saturation was significantly less in athletes compared with controls ( P = 0.002). These data indicate endurance-trained athletes have increased synthesis rates of skeletal muscle IMTG and decreased saturation of skeletal muscle diacylglycerol. Increased synthesis rates are not due to recovery from exercise and are likely adaptations to chronic endurance exercise training.

scholarly journals Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

2012 ◽  
Vol 303 (5) ◽  
pp. E607-E613 ◽  
Author(s):  
Scott M. Chadderdon ◽  
J. Todd Belcik ◽  
Elise Smith ◽  
Lindsay Pranger ◽  
Paul Kievit ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Rhesus Macaques ◽  
Muscle Blood Flow ◽  
Normal Activity ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Activity Restriction ◽  
Capillary Recruitment

Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques ( Macaca mulatta) after sedation with ketamine and during maintenance anesthesia with isoflurane. Thirteen normal-activity (NA) and six activity-restricted (AR) primates underwent contrast-enhanced ultrasound to determine skeletal muscle capillary blood volume (CBV) during an intravenous glucose tolerance test (IVGTT) and during contractile exercise. NO bioactivity was assessed by flow-mediated vasodilation. Although there were no differences in weight, basal glucose, basal insulin, or truncal fat, AR primates were insulin resistant compared with NA primates during an IVGTT (2,225 ± 734 vs. 5,171 ± 3,431 μg·ml−1·min−1, P < 0.05). Peak CBV was lower in AR compared with NA primates during IVGTT (0.06 ± 0.01 vs. 0.12 ± 0.02 ml/g, P < 0.01) and exercise (0.10 ± 0.02 vs. 0.20 ± 0.02 ml/g, P < 0.01), resulting in a lower peak skeletal muscle blood flow in both circumstances. The insulin-mediated changes in CBV correlated inversely with the degree of IR and directly with activity. Flow-mediated dilation was lower in the AR primates (4.6 ± 1.0 vs. 9.8 ± 2.3%, P = 0.01). Thus, activity restriction produces impaired skeletal muscle capillary recruitment during a carbohydrate challenge and contributes to IR in the absence of obesity. Reduced NO bioactivity may be a pathological link between inactivity and impaired capillary function.

Hyperinsulinemic Compensation For Insulin Resistance Occurs Independent Of Elevated Glycemia In Male Dogs

Endocrinology ◽  
2021 ◽  
Author(s):  
Marilyn Ader ◽  
Richard N Bergman
Keyword(s):  
Insulin Resistance ◽  
Subcutaneous Fat ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Primary Element ◽  
Subcutaneous Adiposity ◽  
Hyperinsulinemic Compensation

Abstract Insulin resistance (IR) engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of Type 2 diabetes. The signal which heralds developing IR and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n=58) were fed a hypercaloric, fat-supplemented diet for 6 wks. Dogs underwent MRI to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test (IVGTT) to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and IR at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6-8 pm) or nocturnal glycemia (2-4 am). IR and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.

Decline in insulin action with age in endurance-trained humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2105-2111 ◽  
Author(s):  
Christopher M. Clevenger ◽  
Pamela Parker Jones ◽  
Hirofumi Tanaka ◽  
Douglas R. Seals ◽  
Christopher A. DeSouza
Keyword(s):  
Endurance Exercise ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Intravenous Glucose ◽  
Trained Subjects ◽  
Age Related ◽  
Similar Body

We tested the hypothesis that regular endurance exercise prevents the age-related decline in insulin action typically observed in healthy, sedentary adults. An index of whole body insulin sensitivity (ISI), obtained from minimal model analysis of insulin and glucose concentrations during a frequently sampled intravenous glucose tolerance test, was determined in 126 healthy adults: 25 young [27 ± 1 (SE) yr; 13 men/12 women] and 43 older (59 ± 1 yr; 20/13) sedentary and 25 young (29 ± 1 yr; 12/13) and 33 older (60 ± 1 yr; 20/13) endurance trained. ISI values were lower in the older vs. young adults in both sedentary (−53%; 3.9 ± 0.3 vs. 7.0 ± 0.7 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01) and endurance-trained (−36%; 7.9 ± 0.6 vs. 12.4 ± 1.0 ×10−4min−1 · μU−1 · ml−1; P < 0.01) groups, but the value was 72–102% higher in the trained subjects at either age ( P < 0.01). In subgroup analysis of sedentary and endurance-trained adults with similar body fat levels ( n = 62), the age-related reduction in ISI persisted only in the endurance-trained subjects (12.9 ± 1.9 vs. 8.7 ± 1.2 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01). The results of the present study suggest that habitual endurance exercise does not prevent the age-associated decline insulin action. Moreover, the age-related reduction in ISI in endurance-trained adults appears to be independent of adiposity.

Expression of FOXC2 in adipose and muscle and its association with whole body insulin sensitivity

2004 ◽  
Vol 287 (4) ◽  
pp. E799-E803 ◽  
Author(s):  
Gina B. Di Gregorio ◽  
Rickard Westergren ◽  
Sven Enerback ◽  
Tong Lu ◽  
Philip A. Kern
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Forkhead Transcription Factor ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Tnf Α

FOXC2 is a winged helix/forkhead transcription factor involved in PKA signaling. Overexpression of FOXC2 in the adipose tissue of transgenic mice protected against diet-induced obesity and insulin resistance. We examined the expression of FOXC2 in fat and muscle of nondiabetic humans with varying obesity and insulin sensitivity. There was no relation between body mass index (BMI) and FOXC2 mRNA in either adipose or muscle. There was a strong inverse relation between adipose FOXC2 mRNA and insulin sensitivity, using the frequently sampled intravenous glucose tolerance test ( r = −0.78, P < 0.001). However, there was no relationship between muscle FOXC2 and any measure of insulin sensitivity. To separate insulin resistance from obesity, we examined FOXC2 expression in pairs of subjects who were matched for BMI but who were discordant for insulin sensitivity. Compared with insulin-sensitive subjects, insulin-resistant subjects had threefold higher levels of adipose FOXC2 mRNA ( P = 0.03). In contrast, muscle FOXC2 mRNA expression was no different between insulin-resistant and insulin-sensitive subjects. There was no association of adipose or muscle FOXC2 mRNA with either circulating or adipose-secreted TNF-α, IL-6, leptin, adiponectin, or non-esterified fatty acids. Thus adipose FOXC2 is more highly expressed in insulin-resistant subjects, and this effect is independent of obesity. This association between FOXC2 and insulin resistance may be related to the role of FOXC2 in PKA signaling.

Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults

2002 ◽  
Vol 11 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Donald R. Dengel ◽  
Michael D. Brown ◽  
Robert E. Ferrell ◽  
Thomas H. Reynolds ◽  
Mark A. Supiano
Keyword(s):  
Insulin Action ◽  
Insulin Response ◽  
Exercise Program ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Before And After ◽  
Ace Genotype ◽  
Exercise Induced

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 ± 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (SI), assessed by the frequently sampled intravenous glucose tolerance test, was significantly ( P = 0.0001) increased following AEX. In addition, there was a significant ( P = 0.001) interaction between AEX and ACE genotype. SI increased significantly ( P < 0.05) more in those with the II (2.5 ± 0.8 μU × 10−4 · min−1 · ml−1) ACE genotype compared with both the DD and ID (0.7 ± 0.1 and 0.7 ± 0.2 μU × 10−4 · min−1 · ml−1, respectively) ACE genotypes. Similarly, there was a significant ( P = 0.036) decrease in the acute insulin response to glucose (AIRG) and a significant ( P = 0.05) interaction between AEX and ACE genotype. AIRG decreased significantly ( P < 0.05) more in those with the II (−17.6 ± 5.6 mU/ml) ACE genotype compared with both the DD and ID (−1.4 ± 6.2 and −3.6 ± 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

scholarly journals Insulin Resistance and Adiponectin Levels in Drug-Free Patients with Schizophrenia: A Preliminary Report

2006 ◽  
Vol 51 (6) ◽  
pp. 382-386 ◽  
Author(s):  
Tony A Cohn ◽  
Gary Remington ◽  
Robert B Zipursky ◽  
Azar Azad ◽  
Philip Connolly ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Healthy Volunteers ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
The Mean ◽  
Drug Free

Objective: To compare the insulin sensitivity and adiponectin levels of medication-free patients suffering from schizophrenia or schizoaffective disorder with that of matched healthy volunteers. Method: We evaluated 9 nondiabetic patients aged 26.6 years (median 26 years, range 17 to 41 years) and matched volunteers, using the frequently sampled intravenous glucose tolerance test, minimal model analysis, and fasting adiponectin levels. Results: The mean insulin sensitivity index of the patients was 42% lower than that of the healthy volunteers ( P = 0.026), with inadequate compensation in insulin secretion. Patients with schizophrenia tended to have reduced adiponectin levels ( P = 0.055). Conclusions: By direct measurement, this study provides evidence of insulin resistance and susceptibility to type 2 diabetes in patients with schizophrenia who are free of antipsychotic drugs.

Effect of diet on insulin binding and glucose transport in rat sarcolemmal vesicles

1987 ◽  
Vol 252 (3) ◽  
pp. E420-E425
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
E. Sternlicht ◽  
R. H. Whitson ◽  
S. A. Kaplan
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Intravenous Glucose ◽  
High Affinity ◽  
Sarcolemmal Vesicles

The purpose of this study was to compare the effects of a high-fat, high-sucrose diet (HFS) and a low-fat, high-complex carbohydrate diet (LFC) on glucose tolerance, insulin binding, and glucose transport in rat skeletal muscle. During the intravenous glucose tolerance test, peak glucose values at 5 min were significantly higher in the HFS group; 0-, 20-, and 60-min values were similar. Insulin values were significantly higher in the HFS group at all time points (except 60 min), indicating whole-body insulin resistance. Skeletal muscle was responsible, in part, for this insulin resistance, because specific D-glucose transport in isolated sarcolemmal (SL) vesicles under basal conditions was similar between LFC and HFS rats (35 +/- 5 vs. 32 +/- 4 pmol/mg protein), despite the higher plasma insulin levels. Scatchard analyses of insulin binding curves to sarcolemmal vesicles revealed that the Ka of the high-affinity binding sites was significantly reduced by the HFS diet (0.63 +/- 0.09 vs. 0.35 +/- 0.05 X 10(9) M-1); no other binding changes were noted. Specific D-glucose transport in SL vesicles after maximum insulin stimulation (1 U/kg) was significantly depressed in the HFS group (87 +/- 7 vs. 58 +/- 7 pmol/mg protein), indicating that HFS feeding also caused a postbinding defect. These results indicate that the insulin resistance in skeletal muscle associated with a HFS diet is due to both a decrease in the Ka of the high-affinity insulin receptors and a postbinding defect.

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