PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis

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After a meal, dietary glucose travels through the hepatic portal vein to the liver. A substantial part of this glucose is taken up by liver, which converts it to glycogen which is stored, and lipids which are in part stored and in part secreted as VLDL particles. The rest of the organs receive whatever glucose the liver leaves in circulation, plus the secreted lipids. Hence the liver plays a crucial role in determining the balance of sugar versus lipids in the body after a meal. This balance is very important, because too much glucose in circulation leads to diabetic complications whereas too much VLDL increases risk of atherosclerosis. Little is known about how the liver strikes this balance. We identify here a phosphatase—the PP2A holoenzyme containing the PPP2R5C regulatory subunit—as a regulator of this process. We find that knockdown of PPP2R5C in mouse liver specifically causes it to uptake elevated levels of glucose, and secrete elevated levels of VLDL into circulation. This leads to a phenotype of improved glucose tolerance and insulin sensitivity. The prediction from these functional studies in mice is that elevated levels of PPP2R5C expression should lead to insulin resistance. Indeed, we find that PPP2R5C expression levels are elevated in diabetic patients, or healthy controls with visceral obesity, raising the possibility that dysregulation of PPP2R5C expression in humans may contribute towards metabolic dysfunction.

Vyšlo v časopise: PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005561
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005561

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