PI4KII? regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway.

ABSTRACT: Insulin release by pancreatic ? cells plays a key role in regulating blood glucose levels in humans, and to understand the mechanism for insulin secretion may reveal therapeutic strategies for diabetes. We found that PI4KII? transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose levels than wild-type mice. Glucose-stimulated insulin secretion was significantly reduced in both PI4KII? TG mice and PI4KII?-overexpressing pancreatic ? cell lines. A proximity-based biotin labeling technique, BioID, was used to identify proteins that interact with PI4KII?, and the results revealed that PI4KII? interacts with PKD and negatively regulates its activity. The effect of PI4KII? on insulin secretion was completely rescued by altering PKD activity. PI4KII? overexpression also worsened glucose tolerance in streptozotocin/high-fat diet-induced diabetic mice by impairing insulin secretion. Our study has shed new light on PI4KII? function and mechanism in diabetes and identified PI4KII? as an important regulator of insulin secretion.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC5860104 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature