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• W3185158768 abstract "Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2Akita) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2Akita and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca2+ ATPase (PMCA) and cytotoxic Ca2+ overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP." @default.
• W3185158768 created "2021-08-02" @default.
• W3185158768 creator A5038874883 @default.
• W3185158768 creator A5053609858 @default.
• W3185158768 creator A5059476872 @default.
• W3185158768 creator A5077148102 @default.
• W3185158768 creator A5083575172 @default.
• W3185158768 creator A5086002793 @default.
• W3185158768 creator A5088580577 @default.
• W3185158768 date "2021-07-19" @default.
• W3185158768 modified "2023-09-27" @default.
• W3185158768 title "Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps" @default.
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