| First Author | Bergeron V | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 1 | Pages | 71-77 |
| PubMed ID | 29038309 | Mgi Jnum | J:255151 |
| Mgi Id | MGI:6112889 | Doi | 10.2337/db17-0982 |
| Citation | Bergeron V, et al. (2018) Deletion of Protein Kinase D1 in Pancreatic beta-Cells Impairs Insulin Secretion in High-Fat Diet-Fed Mice. Diabetes 67(1):71-77 |
| abstractText | Betabeta-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 beta-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the beta-cell and plays a critical role in the control of insulin secretion. However, the role of beta-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using beta-cell-specific, inducible PKD1 knockout mice (betaPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding. betaPKD1KO mice under a chow diet presented no significant difference in glucose tolerance or insulin secretion compared with mice expressing the Cre transgene alone; however, when compared with wild-type mice, both groups developed glucose intolerance. Under a high-fat diet, deletion of PKD1 in beta-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 diet-fed betaPKD1KO mice without changes in islet mass. This study demonstrates an essential role for PKD1 in the beta-cell adaptive secretory response to high-fat feeding in mice. |
