Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca²⁺ Sensitivity of Insulin Secretion Vesicles.

ABSTRACT: Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca²⁺ concentrations, suggesting differences in the Ca²⁺ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca²⁺ binding paralog of the β cell Ca²⁺ sensor Syt7, increased by ∼8-fold during β cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS. Precocious Syt4 expression repressed basal insulin secretion but also impaired islet morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels inversely related to the number of readily releasable vesicles. Thus

SUBMITTER: Huang C 

PROVIDER: S-EPMC5962294 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature