Endocrinology, Vol 137, 4644-4649, Copyright © 1996 by Endocrine Society

ARTICLES

Ca2+/calmodulin and cyclic 3,5' adenosine monophosphate control movement of secretory granules through protein phosphorylation/dephosphorylation in the pancreatic beta-cell

M Hisatomi, H Hidaka and I Niki
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.

We observed the movement of insulin granules in living transformed hamster pancreatic beta-cells (HIT T15) with a light microscope, where secretory granules are moving in the cytoplasmic space. Velocity of the typical granule movement was approximately 1.5 microns/sec. A stimulatory concentration of glucose activated the movement of the secretory granules. Forskolin, an activator of adenylate cyclase, increased the movement, resulting in changes in intracellular localization of the granules. Acetylcholine also activated the granule movement, whereas high K+ and tolbutamide, which cause Ca2+ influx through the voltage-dependent Ca2+ channel, had only little effect. The movement was abolished by BAPTA, the intracellular Ca2+-chelator. Activation of protein kinase C by 12-O-tetradecanoyl-phorbol 13-acetate failed to affect this movement. The motile events were inhibited by the calmodulin antagonist, W-7, and dramatically increased by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. These results suggest protein phosphorylation by Ca2+/calmodulin- and cAMP-dependent protein kinases play a positive role in the control of the insulin granule movements, which results in potentiation of insulin release from the pancreatic beta-cell.

This article has been cited by other articles:

				A. S. Goehring, B. S. Pedroja, S. A. Hinke, L. K. Langeberg, and J. D. Scott MyRIP Anchors Protein Kinase A to the Exocyst Complex J. Biol. Chem., November 9, 2007; 282(45): 33155 - 33167. [Abstract] [Full Text] [PDF]

				M. Hao, X. Li, M. A. Rizzo, J. V. Rocheleau, B. M. Dawant, and D. W. Piston Regulation of two insulin granule populations within the reserve pool by distinct calcium sources J. Cell Sci., December 15, 2005; 118(24): 5873 - 5884. [Abstract] [Full Text] [PDF]

				M. Dolz, D. Bailbe, M.-H. Giroix, S. Calderari, M.-N. Gangnerau, P. Serradas, K. Rickenbach, J.-C. Irminger, and B. Portha Restitution of Defective Glucose-Stimulated Insulin Secretion in Diabetic GK Rat by Acetylcholine Uncovers Paradoxical Stimulatory Effect of {beta}-Cell Muscarinic Receptor Activation on cAMP Production Diabetes, November 1, 2005; 54(11): 3229 - 3237. [Abstract] [Full Text] [PDF]

				S. Seino and T. Shibasaki PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis Physiol Rev, October 1, 2005; 85(4): 1303 - 1342. [Abstract] [Full Text] [PDF]

				Y. Uchizono, M. Iwase, U. Nakamura, N. Sasaki, D. Goto, and M. Iida Tacrolimus Impairment of Insulin Secretion in Isolated Rat Islets Occurs at Multiple Distal Sites in Stimulus-Secretion Coupling Endocrinology, May 1, 2004; 145(5): 2264 - 2272. [Abstract] [Full Text] [PDF]

				J. Li, R. Luo, A. Kowluru, and G. Li Novel regulation by Rac1 of glucose- and forskolin-induced insulin secretion in INS-1 {beta}-cells Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E818 - E827. [Abstract] [Full Text] [PDF]

				N. Takahashi, H. Hatakeyama, H. Okado, A. Miwa, T. Kishimoto, T. Kojima, T. Abe, and H. Kasai Sequential exocytosis of insulin granules is associated with redistribution of SNAP25 J. Cell Biol., April 26, 2004; 165(2): 255 - 262. [Abstract] [Full Text] [PDF]

				M. G. Pezzolesi, M. Nam, T. Nagase, T. Klupa, J. S. Dunn, W. M. Mlynarski, S. S. Rich, J. H. Warram, and A. S. Krolewski Examination of Candidate Chromosomal Regions for Type 2 Diabetes Reveals a Susceptibility Locus on Human Chromosome 8p23.1 Diabetes, February 1, 2004; 53(2): 486 - 491. [Abstract] [Full Text]

				I. Niki, T. Niwa, W. Yu, D. Budzko, T. Miki, and T. Senda Ca2+ Influx Does Not Trigger Glucose-Induced Traffic of the Insulin Granules and Alteration of Their Distribution Experimental Biology and Medicine, November 1, 2003; 228(10): 1218 - 1226. [Abstract] [Full Text] [PDF]

				A. Sjoholm, M. Lehtihet, A. M. Efanov, S. V. Zaitsev, P.-O. Berggren, and R. E. Honkanen Glucose Metabolites Inhibit Protein Phosphatases and Directly Promote Insulin Exocytosis in Pancreatic {beta}-Cells Endocrinology, December 1, 2002; 143(12): 4592 - 4598. [Abstract] [Full Text] [PDF]

				J.-C. Henquin, N. Ishiyama, M. Nenquin, M. A. Ravier, and J.-C. Jonas Signals and Pools Underlying Biphasic Insulin Secretion Diabetes, February 1, 2002; 51(90001): S60 - 67. [Abstract] [Full Text] [PDF]

				A. Varadi, E. K. Ainscow, V. J. Allan, and G. A. Rutter Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic {beta}-cells J. Cell Sci., January 11, 2002; 115(21): 4177 - 4189. [Abstract] [Full Text] [PDF]

				Y. Tian and S. G. Laychock Protein Kinase C and Calcium Regulation of Adenylyl Cyclase in Isolated Rat Pancreatic Islets Diabetes, November 1, 2001; 50(11): 2505 - 2513. [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. Tabuchi, H. Yamamoto, K. Matsumoto, K. Ebihara, Y. Takeuchi, K. Fukunaga, H. Hiraoka, Y. Sasaki, M. Shichiri, and E. Miyamoto Regulation of Insulin Secretion by Overexpression of Ca2+/Calmodulin-Dependent Protein Kinase II in Insulinoma MIN6 Cells Endocrinology, July 1, 2000; 141(7): 2350 - 2360. [Abstract] [Full Text] [PDF]

				L. Delahaye, S. Rocchi, and E. Van Obberghen Potential Involvement of FRS2 in Insulin Signaling Endocrinology, February 1, 2000; 141(2): 621 - 628. [Abstract] [Full Text] [PDF]

				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]

				M. E. Carbajal and M. L. Vitale The Cortical Actin Cytoskeleton of Lactotropes as an Intracellular Target for the Control of Prolactin Secretion Endocrinology, December 1, 1997; 138(12): 5374 - 5384. [Abstract] [Full Text] [PDF]

				K. A. Krueger, H. Bhatt, M. Landt, and R. A. Easom Calcium-stimulated Phosphorylation of MAP-2 in Pancreatic beta TC3-cells Is Mediated by Ca2+/Calmodulin-dependent Kinase II J. Biol. Chem., October 24, 1997; 272(43): 27464 - 27469. [Abstract] [Full Text] [PDF]

				Y. Iida, T. Senda, Y. Matsukawa, K. Onoda, J.-I. Miyazaki, H. Sakaguchi, Y. Nimura, H. Hidaka, and I. Niki Myosin light-chain phosphorylation controls insulin secretion at a proximal step in the secretory cascade Am J Physiol Endocrinol Metab, October 1, 1997; 273(4): E782 - E789. [Abstract] [Full Text] [PDF]

				C. Wasmeier and J. C. Hutton Secretagogue-dependent Phosphorylation of the Insulin Granule Membrane Protein Phogrin Is Mediated by cAMP-dependent Protein Kinase J. Biol. Chem., August 17, 2001; 276(34): 31919 - 31928. [Abstract] [Full Text] [PDF]