Dynamin deficiency causes insulin secretion failure and hyperglycemia
Fan Fan, Yumei Wu, Manami Hara, Adam A. Rizk, Chen Ji, Dan Nerad, Natalia A. Tamarina, Xuelin Lou
Abstract
Significance Insulin secretion regulates broad cellular function and glucose homeostasis, and its disruption causes diabetes. Insulin secretion requires granule fusion with the plasma membrane to allow insulin release (called exocytosis). Exocytosis is coupled with robust endocytosis, a process that retrieves materials from the cell surface. There exists an ongoing debate around the contributions of coupled endocytosis to insulin secretion. Here, we investigate this issue in adult mouse β cells by deleting all three mammalian dynamin genes. Interestingly, dynamin triple-knockout β cells still contain abundant insulin granules but cannot release insulin effectively, causing the disrupted glucose homeostasis in vivo. These findings demonstrate the pivotal role of dynamin in insulin secretion by coordinating the “in” and “out” of membrane trafficking in endocrine cells.