Synapsins I and II Are Not Required for Insulin Secretion from Mouse Pancreatic beta-cells
Författare
Summary, in English
Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic beta-cells has also been suggested to be regulated by synapsins. In this study, we have utilized a knock out mouse model with general disruptions of the synapsin I and II genes [synapsin double knockout (DKO)]. Stimulation with 20 mM glucose increased insulin secretion 9-fold in both wild-type (WT) and synapsin DKO islets, whereas secretion in the presence of 70 mM K+ and 1mM glucose was significantly enhanced in the synapsin DKO mice compared to WT. Exocytosis in single beta-cells was investigated using patch clamp. The exocytotic response, measured by capacitance measurements and elicited by a depolarization protocol designed to visualize exocytosis of vesicles from the readily releasable pool and from the reserve pool, was of the same size in synapsin DKO and WT beta-cells. The increase in membrane capacitance corresponding to readily releasable pool was approximately 50fF in both genotypes. We next investigated the voltage-dependent Ca2+ influx. In both WT and synapsin DKO beta-cells the Ca2+ current peaked at 0 mV and measured peak current (I-p) and net charge (Q) were of similar magnitude. Finally, ultrastructural data showed no variation in total number of granules (N-v) or number of docked granules (N-s) between the beta-cells from synapsin DKO mice and WT control. We conclude that neither synapsin I nor synapsin II are directly involved in the regulation of glucose-stimulated insulin secretion and Ca-2-dependent exocytosis in mouse pancreatic beta-cells. (Endocrinology 153: 2112-2119, 2012)
Avdelning/ar
- Diabetes - öcellsexocytos
- Diabetes - Clinical Obesity
- Islet cell physiology
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2012
Språk
Engelska
Sidor
2112-2119
Publikation/Tidskrift/Serie
Endocrinology
Volym
153
Issue
5
Fulltext
- Available as PDF - 754 kB
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Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Endocrinology and Diabetes
Status
Published
Forskningsgrupp
- Diabetes - Islet Cell Exocytosis
- Diabetes - Clinical Obesity
- Islet cell physiology
ISBN/ISSN/Övrigt
- ISSN: 0013-7227