Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance

Journal article


Jocken, Johan W. E., Goossens, Gijs H., Boon, Hanneke, Mason, Rachael R., Essers, Yvonne, Havekes, Bas, Watt, Matthew J., van Loon, Luc J. and Blaak, Ellen E.. (2013). Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance. Diabetologia. 56(10), pp. 2255 - 2265. https://doi.org/10.1007/s00125-013-2995-9
AuthorsJocken, Johan W. E., Goossens, Gijs H., Boon, Hanneke, Mason, Rachael R., Essers, Yvonne, Havekes, Bas, Watt, Matthew J., van Loon, Luc J. and Blaak, Ellen E.
Abstract

Aims/hypothesis: Impaired 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. Methods: Eleven 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⋅O2maxV⋅O2max (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. Results: Hyperinsulinaemia 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/interpretation: Our 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.

Keywordsadipose tissue; diabetes insulin resistance; lipolysis skeletal muscle
Year2013
JournalDiabetologia
Journal citation56 (10), pp. 2255 - 2265
PublisherSpringer
ISSN0012-186X
Digital Object Identifier (DOI)https://doi.org/10.1007/s00125-013-2995-9
Scopus EID2-s2.0-84890120647
Open accessOpen access
Page range2255 - 2265
Research GroupMary MacKillop Institute for Health Research
Publisher's version
Additional information

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Place of publicationGermany
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