Chronic hyperglycaemia is detrimental to pancreatic β-cells by causing impaired insulin secretion and diminished β-cell function through glucotoxicity. Understanding the mechanisms underlying β-cell survival is crucial for the prevention of β-cell failure associated with glucotoxicity. Autophagy is a dynamic lysosomal degradation process that protects organisms against metabolic stress. To date, little is known about the physiological function of autophagy in the pathogenesis of diabetes. In the present study, we explored the roles of autophagy in the survival of pancreatic β-cells exposed to high glucose using pharmacological and genetic manipulation of autophagy. We demonstrated that chronic high glucose increases autophagy in rat INS-1 (832/13) cells and pancreatic islets, and that this increase is enhanced by inhibition of 5′-AMP-activated protein kinase. Our results also indicate that stimulation of autophagy rescues pancreatic β-cells from high-glucose-induced cell death and inhibition of autophagy augments caspase-3 activation, suggesting that autophagy plays a protective role in the survival of pancreatic β-cells. Greater knowledge of the molecular mechanisms linking autophagy and β-cell survival may unveil novel therapeutic targets needed to preserve β-cell function.
Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose
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Diana Han, Byungho Yang, L. Karl Olson, Alexander Greenstein, Seung-Hoon Baek, Kate J. Claycombe, John L. Goudreau, Seong-Woon Yu, Eun-Kyoung Kim; Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose. Biochem J 1 February 2010; 425 (3): 541–551. doi: https://doi.org/10.1042/BJ20090429
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