Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes

Sammanfattning

Glucose-stimulated insulin secretion is biphasic, with a rapid first phase and a slowly developing sustained second phase; both are disturbed in type 2 diabetes (T2D). Biphasic secretion results from vastly different release probabilities of individual insulin granules, but the morphological and molecular basis for this is unclear. Here, we show that human insulin secretion and exocytosis critically depend on the availability of membrane-docked granules and that T2D is associated with a strong reduction in granule docking. Glucose accelerated granule docking, and this effect was absent in T2D. Newly docked granules only slowly acquired release competence; this was regulated by major signaling pathways, but not glucose. Gene expression analysis indicated that key proteins involved in granule docking are downregulated in T2D, and overexpression of these proteins increased granule docking. The findings establish granule docking as an important glucose-dependent step in human insulin secretion that is dysregulated in T2D.

Publicerad i

Cell Metabolism
2018, volym: 27, nummer: 2, sidor: 470-478
Utgivare: CELL PRESS

SLU författare

• Omar Hmeadi, Muhmmad

  • Uppsala universitet

UKÄ forskningsämne

Cell- och molekylärbiologi

Publikationens identifierare

• DOI: https://doi.org/10.1016/j.cmet.2017.12.017

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/131872