title: Synapsins I and II are not required for insulin secretion from mouse pancreatic β-cells.
abstract: Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic β-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 1 mm glucose was significantly enhanced in the synapsin DKO mice compared to WT. Exocytosis in single β-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 β-cells. The increase in membrane capacitance corresponding to readily releasable pool was approximately 50fF in both genotypes. We next investigated the voltage-dependent Ca(2+) influx. In both WT and synapsin DKO β-cells the Ca(2+) 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 β-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 β-cells.
authors.affiliation: Lund University Diabetes Centre, Department of Clinical Sciences in Malmö, Islet Cell Exocytosis, Lund University, 20502 Malmö, Sweden. anna.wendt@med.lu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Wendt
authors.forename: Dina
authors.initials: D
authors.lastname: Speidel
authors.forename: Anders
authors.initials: A
authors.lastname: Danielsson
authors.forename: Jonathan L S
authors.initials: JL
authors.lastname: Esguerra
authors.forename: Inger Lise
authors.initials: IL
authors.lastname: Bogen
authors.forename: S Ivar
authors.initials: SI
authors.lastname: Walaas
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D016704:Synapsins; D005947:Glucose; D002118:Calcium