Role of glycogen metabolism in pancreatic islet beta cell function

Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells

“…Indeed, a role for glycogen in normal β-cell function has recently been excluded by examining the effects of overexpression of PTG and knockdown of glycogen synthase I in mice44. However, this does not exclude a role for glycogen accumulation in diabetes45. Indeed, our data provide evidence that in combination with metabolic dysfunction and changes in autophagy, glycogen accumulation in severe uncompensated diabetes may promote β-cell loss via increased caspase-dependent apoptosis, and thereby enhance the hyperglycaemia.…”

Glycogen phosphorylase inhibition improves beta cell function

“…Earlier studies (Malaisse et al, 1993;Malaisse et al, 1977) suggest that glycogenolysis provides glucose for glycolysis and mitochondrial oxidation in beta cells under starvation conditions and, hence, facilitates insulin release. Under extremely high glucose concentrations, as in diabetes, glycogen accumulation in beta cells may lead to glucotoxicity (Malaisse, 2016;Malaisse et al, 1992). However, a recent study by Mir-Coll provided contradictory results by showing…”

“…The abundance of glycogen in beta cells suggests a unique role for glycogen in these cells. However, the effect of intracellular glycogen content on beta cell function is still debatable (Graf et al, 1981;Malaisse, 2016;Mir-Coll et al, 2016). In the current study, we set out to investigate the effects of increased glycogen levels on beta cells.…”

Does Glycogen Accumulation in Pancreatic Islet Beta Cells Play a Minor or Major Role in the Physiology and Pathology of the Insulin Secretory Response to Glucose?

“…Because of the limit of about 1,500 words imposed on the writing of a "Letter" in Diabetologia, all relevant comments on the findings reported by Mir-Coll et al [1] could not be explicitely presented or even only mentioned in such a letter [2].…”

“…In a letter concerning this article and also published in Diabetologia [2], it was reminded, however, that a role for glycogenolysis in pancreatic beta cells in the regulation of insulin secretion was first proposed in 1967, when it was observed that theophylline stimulates insulin secretion from pancreatic pieces incubated in the absence of extracellular glucose, provided that the pieces of pancreas were obtained from rats infused for 8 -10 h with glucose, whilst such was not the case in pancreatic pieces prepared from euglycemic control rats [3]. The glucose-infused animals were severely hyperglycemic (mean plasma glucose concentration 72 mM) and fine particles of glycogen were histologically demonstrated in their islets.…”