Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather than obesity in the mouse.

Diabetologia
S MuñozF Bosch

Abstract

In adipocytes, triacylglycerol synthesis depends on the formation of glycerol 3-phosphate, which originates either from glucose, through glycolysis, or from lactate, through glyceroneogenesis. However, glucose is traditionally viewed as the main precursor of the glycerol backbone and thus, enhanced glucose uptake would be expected to result in increased triacylglycerol synthesis and contribute to obesity. To further explore this issue, we generated a mouse model with chronically increased glucose uptake in adipose tissue by expressing Gck, which encodes the glucokinase enzyme. Here we show that the production of high levels of glucokinase led to increased adipose tissue glucose uptake and lactate production, improved glucose tolerance and higher whole-body and skeletal muscle insulin sensitivity. There was no parallel increase in glycerol 3-phosphate synthesis in vivo, fat accumulation or obesity. Moreover, at high glucose concentrations, in cultured fat cells overproducing glucokinase, glycerol 3-phosphate synthesis from pyruvate decreased, while glyceroneogenesis increased in fat cells overproducing hexokinase II. These findings indicate that the absence of glucokinase inhibition by glucose 6-phosphate probably led to increas...Continue Reading

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Citations

Oct 28, 2011·Nutrition & Metabolism·Marià Alemany
Apr 11, 2015·Trends in Endocrinology and Metabolism : TEM·Saeed Esmaili, Jacob George
Jul 11, 2018·EMBO Molecular Medicine·Veronica JimenezFatima Bosch
Oct 29, 2020·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Estefania CasanaFatima Bosch

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