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Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance |
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| Authors: | Johan W E Jocken Gijs H Goossens Hanneke Boon Rachael R Mason Yvonne Essers Bas Havekes Matthew J Watt Luc J van Loon Ellen E Blaak |
| Institution: | 1. Department of Human Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre+, PO Box 616, 6200 MD, Maastricht, the Netherlands 2. Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands 3. Department of Physiology, Monash University, Clayton, VIC, Australia 4. Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre+, Maastricht, the Netherlands |
| Abstract: | Aims/hypothesisImpaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men.MethodsEleven NGT men and nine long-term diagnosed type 2 diabetic men (7?±?1 years), matched for age (58?±?2 vs 62?±?2 years), BMI (31.4?±?0.6 vs 30.5?±?0.6 kg/m2) and V ? O 2 max $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ (28.9?±?1.5 vs 29.5?±?2.4 ml kg?1 min?1) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic–euglycaemic clamp (8, 20 and 40 mU m?2 min?1). AT and SM biopsies were collected to investigate underlying mechanisms.ResultsHyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (?7?±?6%, ?13?±?9% and ?27?±?9%) compared with men with NGT (?21?±?7%, ?38?±?8% and ?53?±?8%) (p?=?0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8?±?3.1 vs 30.5?±?2.0 μmol kg body weight?1 min?1; p?<?0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups.Conclusions/interpretationOur results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01680133 |
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