Summary
We have investigated the effects of cAMP enhancing agents on depolarization-induced membrane capacitance increases (ΔCm in single rat pancreatic B-cells. Concentrations of IBMX, 8-CPT cAMP and forskolin, which enhance cAMP and insulin release, all enhance depolarization-induced ΔCm's seen in response to single voltage-clamp pulses and reduce the depression of ΔCm responses often seen with trains of pulses. These effects often occur in the absence of changes in peak Ca2+ current or the total Ca2+ charge entry during the depolarizing pulse. These data suggest that cAMP modulating maneuvers may directly affect the mechanism of insulin granule mobilization into a readily releasible store or fusion at a discharge site.
References
Singer J, Goldberg HM (1970) Evidence for a role of cyclic AMP in neuromuscular transmission. Proc Natl Acad Sci (USA) 64:134–138.
Artalego CR, Ariano MA, Perlman RL, Fox AP (1990) Activation of facilitation calcium channels by D1 dopamine receptors through cAMP/protein kinase A-dependent mechanism. Nature 348:239–242.
Sikdar SK, Zorec R, Mason WT (1990) cAMP directly facilitates Ca2+-induced exocytosis in bovine lactotrophs. FEBS Lett 273:150–154.
Malaisse WJ, Malaisse-Lagae F, Mayhew D (1967) A possible role for the adenylcyclase system in insulin secretion. J Clin Invest 46:1724–1734.
Pipeleers DG, Schmit FC, In'tVeld PA, Maes E, Hooghe-Peters EG, Van de Winkel M, Gepts W (1985) Interplay of nutrients and hormones in the regulation of insulin release. Endocrinology 117:824–833.
Gillis KD, Misler S (1992) Single cell assay of exocytosis from pancreatic islet B-cells. Pflügers Arch (Eur J Physiol) 420:121–123.
Pipeleers D (1987) The biosociology of pancreatic B cells. Diabetologia 30:277–291.
Schmit FC, Pipeleers DG (1985) Regulation of adenosine 3′5′ monophosphate levels in the pancreatic B cell. Endocrinology 117:834–840.
Jones PM, Fyles JM, Howell SL (1986) Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilized by high voltage discharge. FEBS Lett 205:205–209.
Ämmälä C, Ashcroft FM, Rorsman P (1993) Calcium-independent potentiation of insulin release by cyclic AMP in single B-cells. Nature (in press).
Burgoyne RD (1991) Control of exocytosis in adrenal chromaffin cells. Biochim Biophys Acta 1071:174–202.
Llinas R, Gruner JA, Sugimori M, McGuiness TL, Greengard P (1991) Regulation by synapsin I and Ca2+-calmodulin-dependent protein kinase II of transmitter release in squid giant synapse. J Physiol 436:257–282.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gillis, K.D., Misler, S. Enhancers of cytosolic cAMP augment depolarization-induced exocytosis from pancreatic B-cells: evidence for effects distal to Ca2+ entry. Pflugers Arch. 424, 195–197 (1993). https://doi.org/10.1007/BF00374612
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00374612