Journal
CELL METABOLISM
Volume 27, Issue 2, Pages 470-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2017.12.017
Keywords
-
Categories
Funding
- Swedish Science Council
- Diabetes Wellness Network Sweden
- Swedish Diabetes Society
- European Foundation for the Study of Diabetes
- Swedish Society for Medical Research
- Hjarnfonden
- NovoNordisk
- Family Ernfors foundations
- European Foundation for the Study of Diabetes (EFSD)/Lilly Research Fellowship
- Swedish Society for Medical Research (SSMF)
- JDRF [31-2008-416]
- European Foundation for the Study of Diabetes [BI 2014_5, Lilly FS 2016_9] Funding Source: researchfish
- Novo Nordisk Fonden [NNF17OC0027344, NNF17OC0027038, NNF15OC0016260, NNF14OC0010001] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available