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Publication
Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP
supply to calcium pumps.
Authors Bruce JIE, Sánchez-Alvarez R, Sans MD, Sugden SA, Qi N, James AD, Williams JA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Nature communications
Year 2021
Date Published 7/1/2021
Volume : Pages 12 : 4386
PubMed Reference 34282152
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.




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