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Deletion of protein kinase D1 in pancreatic β-cells impairs insulin secretion in high-fat diet-fed mice

Item Type:Article
Title:Deletion of protein kinase D1 in pancreatic β-cells impairs insulin secretion in high-fat diet-fed mice
Creators Name:Bergeron, V., Ghislain, J., Vivot, K., Tamarina, N., Philipson, L.H., Fielitz, J. and Poitout, V.
Abstract:Bβ-cell adaptation to insulin resistance is necessary to maintain glucose homeostasis in obesity. Failure of this mechanism is a hallmark of type 2 diabetes (T2D). Hence, factors controlling functional β-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the β-cell and plays a critical role in the control of insulin secretion. However, the role of β-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using β-cell specific, inducible PKD1 knock-out mice (βPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding. βPKD1KO mice under chow diet presented no significant difference in glucose tolerance or insulin secretion compared to mice expressing the Cre transgene alone; however, when compared to wild-type mice, both groups developed glucose intolerance. Under high-fat diet, deletion of PKD1 in β-cells worsened hyperglycemia, hyperinsulinemia and glucose intolerance. This was accompanied by impaired glucose-induced insulin secretion both in vivo in hyperglycemic clamps and ex vivo in isolated islets from high-fat fed βPKD1KO mice, without changes in islet mass. This study demonstrates an essential role for PKD1 in the β-cell adaptive secretory response to high-fat feeding in mice.
Keywords:Electrophoresis, Polyacrylamide Gel, Glucose Tolerance Test, High-Fat Diet, Insulin, Insulin-Secreting Cells, Knockout Mice, Protein Kinase C, Type 2 Diabetes Mellitus, Western Blotting, Animals, Mice
Publisher:American Diabetes Association
Page Range:71-77
Date:January 2018
Official Publication:https://doi.org/10.2337/db17-0982
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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