Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis

Diabetologia
Joan Mir-CollJoan J Guinovart

Abstract

Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguis...Continue Reading

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Citations

Aug 29, 2016·Diabetologia·Willy J Malaisse
Jun 5, 2013·Molecular and Cellular Endocrinology·Ping JiaoHaiyan Xu
Oct 27, 2016·Canadian Journal of Physiology and Pharmacology·Susmita Barman, Krishnapura Srinivasan
Nov 25, 2016·Nature Communications·Melissa F BreretonFrances M Ashcroft
Dec 13, 2016·FEBS Letters·Lotta E AnderssonPeter Spégel
Apr 15, 2017·British Journal of Pharmacology·Lilla NagyPéter Bai
Jul 21, 2021·The Journal of Biological Chemistry·Iliana López-SoldadoJordi Duran

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