Dynamin deficiency causes insulin secretion failure and hyperglycemia.

Area of Science:

• Cell Biology
• Endocrinology
• Molecular Biology

Background:

• Pancreatic beta cells require extensive membrane recycling for insulin secretion.
• The precise mechanisms of endocytosis in beta cells remain incompletely understood.

Purpose of the Study:

• To investigate the role of dynamin GTPase in clathrin-mediated endocytosis in pancreatic beta cells.
• To determine the impact of dynamin deletion on insulin secretion and glucose homeostasis.

Main Methods:

• Genetic deletion of all three dynamin genes (DNM1, DNM2, DNM3) in mature mouse beta cells.
• Analysis of endocytic intermediates, insulin granule content, and exocytosis.
• Assessment of glucose-stimulated insulin secretion, intracellular calcium responses, and granule docking.

Main Results:

• Dynamin triple deletion severely impaired beta cell endocytosis, creating abnormal plasma membrane intermediates.
• Despite abundant insulin granules, their release was blunted, causing hyperglycemia and glucose intolerance.
• Dynamin deficiency reduced insulin granule exocytosis, intracellular Ca2+ responses, and granule docking, correlated with altered Munc13-1, RIM1 expression, and F-actin.

Conclusions:

• Dynamin is crucial for dense-core vesicle endocytosis and maintaining the secretory capacity of pancreatic beta cells.
• Impaired membrane trafficking due to dynamin absence highlights a risk factor for endocrine failure and diabetes pathogenesis.