Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Citation metadata

From: Journal of Clinical Investigation(Vol. 125, Issue 11)
Publisher: American Society for Clinical Investigation
Document Type: Report
Length: 10,094 words
Lexile Measure: 1500L

Document controls

Main content

Abstract :

Alterations in insulin granule exocytosis and endocytosis are paramount to pancreatic [beta] cell dysfunction in diabetes mellitus. Here, using temporally controlled gene ablation specifically in [beta] cells in mice, we identified an essential role of dynamin 2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis. Dynamin 2 deletion in [beta] cells caused glucose intolerance and substantial reduction of the second phase of glucose-stimulated insulin secretion (GSIS); however, mutant [beta] cells still maintained abundant insulin granules, with no signs of cell surface expansion. Compared with control [beta] cells, real-time capacitance measurements demonstrated that exocytosis- endocytosis coupling was less efficient but not abolished; clathrin-mediated endocytosis (CME) was severely impaired at the step of membrane fission, which resulted in accumulation of clathrin-coated endocytic intermediates on the plasma membrane. Moreover, dynamin 2 ablation in [beta] cells led to striking reorganization and enhancement of actin filaments, and insulin granule recruitment and mobilization were impaired at the later stage of GSIS. Together, our results demonstrate that dynamin 2 regulates insulin secretory capacity and dynamics in vivo through a mechanism depending on CME and F-actin remodeling. Moreover, this study indicates a potential pathophysiological link between endocytosis and diabetes mellitus.

Source Citation

Source Citation   

Gale Document Number: GALE|A434135294