Dataset Information


Deletion of Protein Kinase D1 in Pancreatic β-Cells Impairs Insulin Secretion in High-Fat Diet-Fed Mice.

ABSTRACT: Ββ-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 knockout mice (βPKD1KO), we examined the role of β-cell PKD1 under basal conditions and during high-fat feeding. βPKD1KO 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 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 diet-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.

SUBMITTER: Bergeron V 

PROVIDER: S-EPMC5741145 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2009-01-01 | S-EPMC2638021 | BioStudies
1000-01-01 | S-EPMC3460483 | BioStudies
1000-01-01 | S-EPMC2877560 | BioStudies
1000-01-01 | S-EPMC3121422 | BioStudies
2019-01-01 | S-EPMC6307965 | BioStudies
1000-01-01 | S-EPMC5025848 | BioStudies
1000-01-01 | S-EPMC1820733 | BioStudies
1000-01-01 | S-EPMC3386109 | BioStudies
2012-01-01 | S-EPMC6101215 | BioStudies
2016-01-01 | S-EPMC4779402 | BioStudies