Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 309, Issue 5, Pages R510-R524Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00228.2014
Keywords
bariatric surgery; insulin sensitivity; weight loss
Categories
Funding
- Danish Ministry of Science, Technology and Innovation
- Danish Council for Independent Research Medical Sciences (FSS)
- Novo Nordisk Foundation
- European Foundation for the study of Diabetes (EFSD)
- Strategic Counsel for the Capital Area of Copenhagen (Denmark)
- Danish Agency for Science, Technology and Innovation
- Novo Nordisk A/S
- Danish Diabetes Academy - Novo Nordisk Foundation
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
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Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose-tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 wk and 3 and 12 mo after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 mo postsurgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4, as well as insulin-induced changes in phosphorylation of Akt and glycogen synthase activity were enhanced 12 mo postsurgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4, and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC, as well as insulin-induced changes in phosphorylation of Akt and TBC1D4, were enhanced 12 mo postsurgery. Adipose tissue from glucose-tolerant subjects was the most responsive to RYGB compared with type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin-sensitive phenotype of skeletal muscle and adipose tissue appears to contribute to the improved whole body insulin action following a substantial weight loss after RYGB.
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