A link between hepatic glucose production and peripheral energy metabolism via hepatokines

Abstract Type 2 diabetes is characterized by a deterioration of glucose tolerance, which associates insulin resistance of glucose uptake by peripheral tissues and increased endogenous glucose production. Here we report that the specific suppression of hepatic glucose production positively modulates...

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Published inMolecular metabolism (Germany) Vol. 3; no. 5; pp. 531 - 543
Main Authors Abdul-Wahed, Aya, Gautier-Stein, Amandine, Casteras, Sylvie, Soty, Maud, Roussel, Damien, Romestaing, Caroline, Guillou, Hervé, Tourette, Jean-André, Pleche, Nicolas, Zitoun, Carine, Gri, Blandine, Sardella, Anne, Rajas, Fabienne, Mithieux, Gilles
Format Journal Article
LanguageEnglish
Published Germany Elsevier GmbH 01.08.2014
Elsevier
Subjects
Endocrinology & Metabolism
Endogenous glucose production
Energy expenditure
Hepatokines
Life Sciences
Liver
Neurons and Cognition
Obesity
Original
Type 2 diabetes
Type 2 diabetes
Energy expenditure
Obesity
Endogenous glucose production
Hepatokines
Liver
endogenous glucose production
hepatokines
type 2 diabetes
KEY WORDS: liver
energy expenditure
obesity
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Summary:Abstract Type 2 diabetes is characterized by a deterioration of glucose tolerance, which associates insulin resistance of glucose uptake by peripheral tissues and increased endogenous glucose production. Here we report that the specific suppression of hepatic glucose production positively modulates whole-body glucose and energy metabolism. We used mice deficient in liver glucose-6 phosphatase that is mandatory for endogenous glucose production. When they were fed a high fat/high sucrose diet, they resisted the development of diabetes and obesity due to the activation of peripheral glucose metabolism and thermogenesis. This was linked to the secretion of hepatic hormones like fibroblast growth factor 21 and angiopoietin-like factor 6. Interestingly, the deletion of hepatic glucose-6 phosphatase in previously obese and insulin-resistant mice resulted in the rapid restoration of glucose and body weight controls. Therefore, hepatic glucose production is an essential lever for the control of whole-body energy metabolism during the development of obesity and diabetes.
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ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2014.05.005