Endocrinology, Vol 117, 834-840, Copyright © 1985 by Endocrine Society

ARTICLES

Regulation of adenosine 3',5'-monophosphate levels in the pancreatic B cell

FC Schuit and DG Pipeleers

The poor glucose-induced insulin release from single purified B cells has been attributed, in part, to the low cellular cAMP levels. The present study demonstrates that isolated B cells exhibit a markedly lower cAMP formation than B cells lodged in intact islets and suggest that this deficiency is caused by their separation from glucagon- containing A cells. cAMP levels in purified B cells are rapidly and potently elevated by glucagon from 10(-10) M on, reaching the values of islet B cells at 10(-9) M. In contrast, exogenous glucagon stimulates cAMP formation in isolated islets only from 3.10(-9) M on, suggesting that endogenously released glucagon is mainly responsible for the higher cAMP levels in islet B cells. Somatostatin counteracts glucagon- induced cAMP production in purified B cells and, therefore, has also the potential to mediate an intra-islet regulation of B cell functions. Neither insulin nor pancreatic polypeptide affect cAMP formation in pancreatic B cells. Glucose alone does not influence cAMP levels in purified B cells, but enhances glucagon-induced cAMP formation in these cells. The glucose-dependent increase in islet cAMP is therefore not considered as the nutrient-induced mediator for hormone release but as a minor amplification of the glucagon-dependent signal. Experiments on reaggregated islet cells permit the reconstruction of the events which regulate cAMP levels in isolated islets. Further support is hereby given to the hypothesis that a normal glucose-induced insulin release from intact islets requires the simultaneous synarchic participation of a nutrient-dependent and a hormone-dependent messenger system.

This article has been cited by other articles:

				G. Kang, O. G Chepurny, M. J Rindler, L. Collis, Z. Chepurny, W.-h. Li, M. Harbeck, M. W Roe, and G. G Holz A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic {beta} cells J. Physiol., July 1, 2005; 566(1): 173 - 188. [Abstract] [Full Text] [PDF]

				E Grapengiesser, H Dansk, and B Hellman External ATP triggers Ca2+ signals suited for synchronization of pancreatic {beta}-cells J. Endocrinol., April 1, 2005; 185(1): 69 - 79. [Abstract] [Full Text] [PDF]

				I. Kharroubi, L. Ladriere, A. K. Cardozo, Z. Dogusan, M. Cnop, and D. L. Eizirik Free Fatty Acids and Cytokines Induce Pancreatic {beta}-Cell Apoptosis by Different Mechanisms: Role of Nuclear Factor-{kappa}B and Endoplasmic Reticulum Stress Endocrinology, November 1, 2004; 145(11): 5087 - 5096. [Abstract] [Full Text] [PDF]

				B. Hellman, H. Dansk, and E. Grapengiesser Pancreatic {beta}-cells communicate via intermittent release of ATP Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E759 - E765. [Abstract] [Full Text] [PDF]

				M. I. Darville, S. Terryn, and D. L. Eizirik An Octamer Motif Is Required for Activation of the Inducible Nitric Oxide Synthase Promoter in Pancreatic {beta}-Cells Endocrinology, March 1, 2004; 145(3): 1130 - 1136. [Abstract] [Full Text] [PDF]

				I. Lundquist, P. Alm, A. Salehi, R. Henningsson, E. Grapengiesser, and B. Hellman Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic {beta}-cells Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1055 - E1063. [Abstract] [Full Text] [PDF]

				B. W. Kahan, L. M. Jacobson, D. A. Hullett, J. M. Ochoada, T. D. Oberley, K. M. Lang, and J. S. Odorico Pancreatic Precursors and Differentiated Islet Cell Types From Murine Embryonic Stem Cells: An In Vitro Model to Study Islet Differentiation Diabetes, August 1, 2003; 52(8): 2016 - 2024. [Abstract] [Full Text] [PDF]

				B. Kutlu, M. I. Darville, A. K. Cardozo, and D. L. Eizirik Molecular Regulation of Monocyte Chemoattractant Protein-1 Expression in Pancreatic {beta}-Cells Diabetes, February 1, 2003; 52(2): 348 - 355. [Abstract] [Full Text] [PDF]

				K. Moens, V. Berger, J.-M. Ahn, C. Van Schravendijk, V. J. Hruby, D. Pipeleers, and F. Schuit Assessment of the Role of Interstitial Glucagon in the Acute Glucose Secretory Responsiveness of In Situ Pancreatic {beta}-Cells Diabetes, March 1, 2002; 51(3): 669 - 675. [Abstract] [Full Text] [PDF]

				C. B. Wollheim and P. Maechler {beta}-Cell Mitochondria and Insulin Secretion: Messenger Role of Nucleotides and Metabolites Diabetes, February 1, 2002; 51(90001): S37 - 42. [Abstract] [Full Text] [PDF]

				P. Bergsten Role of Oscillations in Membrane Potential, Cytoplasmic Ca2+, and Metabolism for Plasma Insulin Oscillations Diabetes, February 1, 2002; 51(90001): S171 - 176. [Abstract] [Full Text] [PDF]

				Y. Kashima, T. Miki, T. Shibasaki, N. Ozaki, M. Miyazaki, H. Yano, and S. Seino Critical Role of cAMP-GEFII{middle dot}Rim2 Complex in Incretin-potentiated Insulin Secretion J. Biol. Chem., November 30, 2001; 276(49): 46046 - 46053. [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]

				M. I. Darville and D. L. Eizirik Cytokine Induction of Fas Gene Expression in Insulin-Producing Cells Requires the Transcription Factors NF-{kappa}B and C/EBP Diabetes, August 1, 2001; 50(8): 1741 - 1748. [Abstract] [Full Text] [PDF]

				B. Lee and S. G. Laychock Regulation of Inositol Trisphosphate Receptor Isoform Expression in Glucose-Desensitized Rat Pancreatic Islets: Role of Cyclic Adenosine 3',5'-Monophosphate and Calcium Endocrinology, April 1, 2000; 141(4): 1394 - 1402. [Abstract] [Full Text] [PDF]

				M. I. Darville, Y.-S. Ho, and D. L. Eizirik NF-{kappa}B Is Required for Cytokine-Induced Manganese Superoxide Dismutase Expression in Insulin-Producing Cells Endocrinology, January 1, 2000; 141(1): 153 - 162. [Abstract] [Full Text] [PDF]

				H.-P. Bode, B. Moormann, R. Dabew, and B. Göke Glucagon-Like Peptide 1 Elevates Cytosolic Calcium in Pancreatic {beta}-Cells Independently of Protein Kinase A Endocrinology, September 1, 1999; 140(9): 3919 - 3927. [Abstract] [Full Text]

				V. Serre, W. Dolci, E. Schaerer, L. Scrocchi, D. Drucker, S. Efrat, and B. Thorens Exendin-(9-39) Is an Inverse Agonist of the Murine Glucagon-Like Peptide-1 Receptor: Implications for Basal Intracellular Cyclic Adenosine 3',5'-Monophosphate Levels and {beta}-Cell Glucose Competence Endocrinology, November 1, 1998; 139(11): 4448 - 4454. [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]

				Z. Ling, M.-C. Chen, A. Smismans, D. Pavlovic, F. Schuit, D. L. Eizirik, and D. G. Pipeleers Intercellular Differences in Interleukin 1{beta}-Induced Suppression of Insulin Synthesis and Stimulation of Noninsulin Protein Synthesis by Rat Pancreatic {beta}-Cells Endocrinology, April 1, 1998; 139(4): 1540 - 1545. [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]

				A. Y. Grupping, M. Cnop, C. F. H. Van Schravendijk, J. C. Hannaert, Th. J. C. Van Berkel, and D. G. Pipeleers Low Density Lipoprotein Binding and Uptake by Human and Rat Islet {beta} Cells Endocrinology, October 1, 1997; 138(10): 4064 - 4068. [Abstract] [Full Text] [PDF]

				B. Thorens, N. Dériaz, D. Bosco, A. DeVos, D. Pipeleers, F. Schuit, P. Meda, and A.ée Porret Protein Kinase A-dependent Phosphorylation of GLUT2 in Pancreatic beta Cells J. Biol. Chem., April 5, 1996; 271(14): 8075 - 8081. [Abstract] [Full Text] [PDF]

				F. Schuit and D. Pipeleers Differences in adrenergic recognition by pancreatic A and B cells Science, May 16, 1986; 232(4752): 875 - 877. [Abstract] [PDF]