Endocrinology, Vol 135, 191-199, Copyright © 1994 by Endocrine Society

ARTICLES

The role of protein kinase-C in signal transduction through vasopressin and acetylcholine receptors in pancreatic B-cells from normal mouse

ZY Gao, P Gilon and JC Henquin
Unite d'Endocrinologie et Metabolisme, Faculty of Medicine, University of Louvain, Brussels, Belgium.

The role of protein kinase-C (PKC) in the potentiation of insulin release by arginine vasopressin (AVP) and acetylcholine (ACh) was investigated with normal mouse islets. The islets were submitted to a short term (30-min) or long term (22-h) treatment with phorbol 12- myristate 13-acetate (PMA) to stimulate acutely or down-regulate PKC before being stimulated by AVP or ACh. Control islets were treated with the inactive 4 alpha-phorbol 12,13-didecanoate. In the presence of 15 mM glucose and 2.5 mM Ca2+, AVP and ACh stimulated inositol phosphate (IP) formation, increased cytoplasmic Ca2+ (Cai2+), and potentiated insulin release. These effects were greater with ACh than with AVP, in particular on Cai2+, which was scarcely affected by AVP. In the absence of extracellular Ca2+, only ACh induced a short-lived increase in Cai2+ and insulin. Acute treatment with PMA in the presence of extracellular Ca2+ strongly increased insulin release in spite of a marked lowering of Cai2+. Under these conditions, the effects of AVP and ACh on IP production and Cai2+ were practically abolished, and only ACh transiently increased insulin release. In the absence of Ca2+, the small mobilization of Cai2+ by ACh triggered a peak of insulin, whereas a similar mobilization of Cai2+ by AVP was ineffective on insulin. After long term treatment of the islets with PMA, AVP normally increased IP formation, but did not affect insulin release. The effect of ACh on IP was still inhibited. However, ACh produced a marked transient increase in Cai2+, with a small transient release of insulin. The releasing effect of ACh was also inhibited in the absence of Ca2+. In conclusion, PKC plays a dual role in the B-cell responses to ACh and AVP. Its activation is necessary for the sustained potentiation of insulin release that both agents produce. This effect probably results from a sensitization of the secretory machinery to Cai2+, the triggering signal. PKC also exerts a negative feedback control on the signal transduction mechanisms involving phospholipase-C, but the ACh and AVP responses are not equally affected by this feedback.

This article has been cited by other articles:

				M. Gilbert, S.-R. Jung, B. J. Reed, and I. R. Sweet Islet Oxygen Consumption and Insulin Secretion Tightly Coupled to Calcium Derived from L-type Calcium Channels but Not from the Endoplasmic Reticulum J. Biol. Chem., September 5, 2008; 283(36): 24334 - 24342. [Abstract] [Full Text] [PDF]

				A.-M. O'Carroll, G. M Howell, E. M Roberts, and S. J Lolait Vasopressin potentiates corticotropin-releasing hormone-induced insulin release from mouse pancreatic {beta}-cells J. Endocrinol., May 1, 2008; 197(2): 231 - 239. [Abstract] [Full Text] [PDF]

				N. Warwar, S. Efendic, C.-G. Ostenson, E. P. Haber, E. Cerasi, and R. Nesher Dynamics of Glucose-Induced Localization of PKC Isoenzymes in Pancreatic {beta}-Cells: Diabetes-Related Changes in the GK Rat Diabetes, March 1, 2006; 55(3): 590 - 599. [Abstract] [Full Text] [PDF]

				S. Barg and P. Rorsman Insulin Secretion: A High-affinity Ca2+ Sensor After All? J. Gen. Physiol., November 29, 2004; 124(6): 623 - 625. [Full Text] [PDF]

				M. Schaefer, H. Mischak, S. Schnell, A. Griese, R. Iakubov, G. Riepenhausen, and C. Schofl Mechanisms of Arginine-Vasopressin-Induced Ca2+ Oscillations in {beta}-Cells (HIT-T15): A Role for Oscillating Protein Kinase C Endocrinology, October 1, 2004; 145(10): 4635 - 4644. [Abstract] [Full Text] [PDF]

				G. C. Yaney, J. M. Fairbanks, J. T. Deeney, H. M. Korchak, K. Tornheim, and B. E. Corkey Potentiation of insulin secretion by phorbol esters is mediated by PKC-alpha and nPKC isoforms Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E880 - E888. [Abstract] [Full Text] [PDF]

				P. Gilon and J.-C. Henquin Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic {beta}-Cell Function Endocr. Rev., October 1, 2001; 22(5): 565 - 604. [Abstract] [Full Text] [PDF]

				H. Cherif, B. Reusens, S. Dahri, and C. Remacle A Protein-Restricted Diet during Pregnancy Alters in Vitro Insulin Secretion from Islets of Fetal Wistar Rats J. Nutr., May 1, 2001; 131(5): 1555 - 1559. [Abstract] [Full Text]

				P. M. Jones and S. J. Persaud Protein Kinases, Protein Phosphorylation, and the Regulation of Insulin Secretion from Pancreatic {beta}-Cells. Endocr. Rev., August 1, 1998; 19(4): 429 - 461. [Abstract] [Full Text] [PDF]

				J. Vadakekalam, M. E. Rabaglia, and S. A. Metz Interleukin-1beta inhibits phospholipase C and insulin secretion at sites apart from KATP channel Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E942 - E950. [Abstract] [Full Text] [PDF]