Diabetes, Vol 39, Issue 5 634-638, Copyright © 1990 by American Diabetes Association

ARTICLES

Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells

SE Kahn, DA D'Alessio, MW Schwartz, WY Fujimoto, JW Ensinck, GJ Taborsky and D Porte
Department of Medicine, University of Washington, Seattle.

Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal beta-cell secretory granules. To determine whether IAPP is a pancreatic secretory product, we measured the quantity of IAPP-like immunoreactivity (IAPP-LI), insulin, and glucagon released into 5 ml of incubation medium during a 2-h incubation of monolayer cultures (n = 5) of neonatal (3- to 5-day-old) Sprague-Dawley rat pancreases under three conditions: 1.67 mM glucose, 16.7 mM glucose, and 16.7 mM glucose plus 10 mM arginine and 0.1 mM isobutylmethylxanthine (IBMX). The quantity of IAPP-LI, insulin, and glucagon in the cell extract was also determined. Mean +/- SE IAPP-LI in the incubation medium increased from 0.041 +/- 0.003 pmol in 1.67 mM glucose to 0.168 +/- 0.029 pmol in 16.7 mM glucose (P less than 0.05) and 1.02 +/- 0.06 pmol in 16.7 mM glucose plus arginine and IBMX (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Insulin secretion increased similarly from 4.34 +/- 0.27 to 20.2 +/- 0.6 pmol (P less than 0.05) and then to 135 +/- 5 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Glucagon release tended to decrease with the increase in glucose concentration (0.39 +/- 0.01 vs. 0.33 +/- 0.02 pmol, P less than 0.1), whereas with the addition of arginine and IBMX to high glucose, glucagon release increased to 1.32 +/- 0.03 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose).(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Marzban, A. Tomas, T. C. Becker, L. Rosenberg, J. Oberholzer, P. E. Fraser, P. A. Halban, and C. B. Verchere Small Interfering RNA-Mediated Suppression of Proislet Amyloid Polypeptide Expression Inhibits Islet Amyloid Formation and Enhances Survival of Human Islets in Culture Diabetes, November 1, 2008; 57(11): 3045 - 3055. [Abstract] [Full Text] [PDF]

				S. Casas, R. Gomis, F. M. Gribble, J. Altirriba, S. Knuutila, and A. Novials Impairment of the Ubiquitin-Proteasome Pathway Is a Downstream Endoplasmic Reticulum Stress Response Induced by Extracellular Human Islet Amyloid Polypeptide and Contributes to Pancreatic {beta}-Cell Apoptosis Diabetes, September 1, 2007; 56(9): 2284 - 2294. [Abstract] [Full Text] [PDF]

				A. Novials, L. Rodriguez-Manas, A. Chico, M. El Assar, S. Casas, and R. Gomis Amylin and Hypertension: Association of an Amylin -G132A Gene Mutation and Hypertension in Humans and Amylin-Induced Endothelium Dysfunction in Rats J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1446 - 1450. [Abstract] [Full Text] [PDF]

				S. Zraika, R. L. Hull, J. Udayasankar, A. Clark, K. M. Utzschneider, J. Tong, F. Gerchman, and S. E. Kahn Identification of the Amyloid-Degrading Enzyme Neprilysin in Mouse Islets and Potential Role in Islet Amyloidogenesis Diabetes, February 1, 2007; 56(2): 304 - 310. [Abstract] [Full Text] [PDF]

				L. Marzban, C. J. Rhodes, D. F. Steiner, L. Haataja, P. A. Halban, and C. B. Verchere Impaired NH2-Terminal Processing of Human Proislet Amyloid Polypeptide by the Prohormone Convertase PC2 Leads to Amyloid Formation and Cell Death. Diabetes, August 1, 2006; 55(8): 2192 - 2201. [Abstract] [Full Text] [PDF]

				L. Marzban, G. Trigo-Gonzalez, and C. B. Verchere Processing of Pro-Islet Amyloid Polypeptide in the Constitutive and Regulated Secretory Pathways of {beta} Cells Mol. Endocrinol., August 1, 2005; 19(8): 2154 - 2163. [Abstract] [Full Text] [PDF]

				J. F. Paulsson and G. T. Westermark Aberrant Processing of Human Proislet Amyloid Polypeptide Results in Increased Amyloid Formation Diabetes, July 1, 2005; 54(7): 2117 - 2125. [Abstract] [Full Text] [PDF]

				L. Marzban, G. Soukhatcheva, and C. B. Verchere Role of Carboxypeptidase E in Processing of Pro-Islet Amyloid Polypeptide in {beta}-Cells Endocrinology, April 1, 2005; 146(4): 1808 - 1817. [Abstract] [Full Text] [PDF]

				R. L. Hull, G. T. Westermark, P. Westermark, and S. E. Kahn Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3629 - 3643. [Abstract] [Full Text] [PDF]

				S. Andrikopoulos, R. L. Hull, C. B. Verchere, F. Wang, S. M. Wilbur, T. N. Wight, L. Marzban, and S. E. Kahn Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E418 - E424. [Abstract] [Full Text]

				R. Dacquin, R. A. Davey, C. Laplace, R. Levasseur, H. A. Morris, S. R. Goldring, S. Gebre-Medhin, D. L. Galson, J. D. Zajac, and G. Karsenty Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo J. Cell Biol., February 16, 2004; 164(4): 509 - 514. [Abstract] [Full Text] [PDF]

				L. Marzban, G. Trigo-Gonzalez, X. Zhu, C. J. Rhodes, P. A. Halban, D. F. Steiner, and C. B. Verchere Role of {beta}-Cell Prohormone Convertase (PC)1/3 in Processing of Pro-Islet Amyloid Polypeptide Diabetes, January 1, 2004; 53(1): 141 - 148. [Abstract] [Full Text] [PDF]

				C. Panagiotopoulos, H. Qin, R. Tan, and C. B. Verchere Identification of a {beta}-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes Diabetes, November 1, 2003; 52(11): 2647 - 2651. [Abstract] [Full Text] [PDF]

				R. G. Bennett, F. G. Hamel, and W. C. Duckworth An Insulin-Degrading Enzyme Inhibitor Decreases Amylin Degradation, Increases Amylin-Induced Cytotoxicity, and Increases Amyloid Formation in Insulinoma Cell Cultures Diabetes, September 1, 2003; 52(9): 2315 - 2320. [Abstract] [Full Text] [PDF]

				T. A. Buchanan, A. H. Xiang, R. K. Peters, S. L. Kjos, A. Marroquin, J. Goico, C. Ochoa, S. Tan, K. Berkowitz, H. N. Hodis, et al. Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women Diabetes, September 1, 2002; 51(9): 2796 - 2803. [Abstract] [Full Text] [PDF]

				N. G. Knowles, M. A. Landchild, W. Y. Fujimoto, and S. E. Kahn Insulin and Amylin Release Are Both Diminished in First-Degree Relatives of Subjects With Type 2 Diabetes Diabetes Care, February 1, 2002; 25(2): 292 - 297. [Abstract] [Full Text] [PDF]

				F. Wang, R. L. Hull, J. Vidal, M. Cnop, and S. E. Kahn Islet Amyloid Develops Diffusely Throughout the Pancreas Before Becoming Severe and Replacing Endocrine Cells Diabetes, November 1, 2001; 50(11): 2514 - 2520. [Abstract] [Full Text] [PDF]

				S. E. Kahn The Importance of {beta}-Cell Failure in the Development and Progression of Type 2 Diabetes J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4047 - 4058. [Full Text] [PDF]

				M. Hoenig, G. Hall, D. Ferguson, K. Jordan, M. Henson, K. Johnson, and T. O'Brien A Feline Model of Experimentally Induced Islet Amyloidosis Am. J. Pathol., December 1, 2000; 157(6): 2143 - 2150. [Abstract] [Full Text] [PDF]

				H. Mulder, S. Gebre-Medhin, C. Betsholtz, F. Sundler, and B. Ahren Islet amyloid polypeptide (amylin)-deficient mice develop a more severe form of alloxan-induced diabetes Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E684 - E691. [Abstract] [Full Text] [PDF]

				C. J. Dechenes, C. B. Verchere, S. Andrikopoulos, and S. E. Kahn Human aging is associated with parallel reductions in insulin and amylin release Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E785 - E791. [Abstract] [Full Text] [PDF]

				M. Clodi, K. Thomaseth, G. Pacini, K. Hermann, A. Kautzky-Willer, W. Waldhausl, R. Prager, and B. Ludvik Distribution and kinetics of amylin in humans Am J Physiol Endocrinol Metab, May 1, 1998; 274(5): E903 - E908. [Abstract] [Full Text] [PDF]

				U. Arnelo, J. Permert, J. Larsson, R. D. Reidelberger, C. Arnelo, and T. E. Adrian Chronic Low Dose Islet Amyloid Polypeptide Infusion Reduces Food Intake, But Does Not Influence Glucose Metabolism, in Unrestrained Conscious Rats: Studies Using a Novel Aortic Catheterization Technique Endocrinology, October 1, 1997; 138(10): 4081 - 4085. [Abstract] [Full Text] [PDF]

				P. J. Wookey, Z. Cao, R. C.I. van Geenen, M. Voskuil, I. A. Darby, R. Komers, and M. E. Cooper Increased Density of Renal Amylin Binding Sites in Experimental Hypertension Hypertension, September 1, 1997; 30(3): 455 - 460. [Abstract] [Full Text]

				M. A. Deeg and C. B. Verchere Regulation of Glycosylphosphatidylinositol-Specific Phospholipase D Secretion from {beta}TC3 cells Endocrinology, February 1, 1997; 138(2): 819 - 826. [Abstract] [Full Text] [PDF]

				C. B. Verchere, M. Paoletta, M. Neerman-Arbez, K. Rose, J.-C. Irminger, R. L. Gingerich, S. E. Kahn, and P. A. Halban Des-(, , , , )C-Peptide. A NOVEL SECRETORY PRODUCT OF THE RAT PANCREATIC BETA CELL PRODUCED BY TRUNCATION OF PROINSULIN CONNECTING PEPTIDE IN SECRETORY GRANULES J. Biol. Chem., November 1, 1996; 271(44): 27475 - 27481. [Abstract] [Full Text] [PDF]

				K. Park and C. B. Verchere Identification of a Heparin Binding Domain in the N-terminal Cleavage Site of Pro-islet Amyloid Polypeptide. IMPLICATIONS FOR ISLET AMYLOID FORMATION J. Biol. Chem., May 11, 2001; 276(20): 16611 - 16616. [Abstract] [Full Text] [PDF]