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Updated: Feb 12, 2026

Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas
Published on: July 25, 2025
PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway
Lunfeng Zhang1,2, Jiangmei Li1,3, Panpan Zhang3
11National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.
Abstract:
Insulin release by pancreatic β 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 PI4KIIα 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 PI4KIIα TG mice and PI4KIIα-overexpressing pancreatic β cell lines. A proximity-based biotin labeling technique, BioID, was used to identify proteins that interact with PI4KIIα, and the results revealed that PI4KIIα interacts with PKD and negatively regulates its activity. The effect of PI4KIIα on insulin secretion was completely rescued by altering PKD activity. PI4KIIα overexpression also worsened glucose tolerance in streptozotocin/high-fat diet-induced diabetic mice by impairing insulin secretion. Our study has shed new light on PI4KIIα function and mechanism in diabetes and identified PI4KIIα as an important regulator of insulin secretion.
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