Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
| Autor: | Muhmmad Omar-Hmeadi, Peng Yin, Petter Vikman, Sebastian Barg, Nikhil R. Gandasi, Emilia Ottosson Laakso |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Type 2 diabetes Cytoplasmic Granules Exocytosis 03 medical and health sciences Internal medicine Diabetes mellitus Insulin-Secreting Cells Insulin Secretion medicine Humans Secretion Insulin secretion Molecular Biology Glycated Hemoglobin Chemistry Granule (cell biology) Cell Biology medicine.disease 030104 developmental biology Endocrinology Somatostatin Glucose Diabetes Mellitus Type 2 Gene Expression Regulation Docking (molecular) |
| Zdroj: | Cell metabolism. 27(2) |
| ISSN: | 1932-7420 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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