Diabetes, Vol 40, Issue 3 327-333, Copyright © 1991 by American Diabetes Association

ARTICLES

Content of CoA-esters in perifused rat islets stimulated by glucose and other fuels

Y Liang and FM Matschinsky
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104-6015.

Fluorometry and high-performance liquid chromatography were used to measure the content of free CoA and the esters of acetate, malonate, succinate, and long-chain fatty acids in isolated perifused rat pancreatic islets exposed to 25 mM glucose or a mixture of fuels (25 mM glucose plus 10 mM glutamine, 10 mM lactate, and 1 mM pyruvate) to assess the role of intermediates of lipid metabolism as candidate metabolic coupling factors in the mechanism of fuel-induced insulin secretion. Insulin secretion was stimulated in a biphasic manner with the fuel mixture, showing twice the potency compared with high glucose alone. Islets perifused for 3 min with high glucose alone or the fuel mixture compared with 2.5 mM glucose showed a significant increase in malonyl-CoA and succinyl-CoA and a decrease in acetyl-CoA. Free CoA and long-chain acyl-CoA levels were unaltered. Perifused islets stimulated with 25 mM glucose for 30 min showed a significant increase in succinyl-CoA and long-chain acyl-CoA and decrease in acetyl-CoA, whereas malonyl-CoA was not affected. However, when islets were stimulated by the fuel mixture for 30 min, malonyl-CoA was maintained at a high level, and the change in succinyl-CoA and long-chain acyl-CoA was similar to that observed in islets stimulated with 25 mM glucose alone. The acetyl-CoA concentration in the islets stimulated with the fuel mixture decreased slightly. These results confirm the viability of the hypothesis that malonyl-CoA and long-chain acyl-CoA serve as metabolic coupling factors in signal transduction when islets are stimulated by high glucose or glucose combined with other fuels.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. MacDonald Synergistic Potent Insulin Release by Combinations of Weak Secretagogues in Pancreatic Islets and INS-1 Cells J. Biol. Chem., March 2, 2007; 282(9): 6043 - 6052. [Abstract] [Full Text] [PDF]

				C. J. Nolan, M. S.R. Madiraju, V. Delghingaro-Augusto, M.-L. Peyot, and M. Prentki Fatty Acid Signaling in the {beta}-Cell and Insulin Secretion Diabetes, December 1, 2006; 55(Supplement_2): S16 - S23. [Abstract] [Full Text] [PDF]

				L. Herrero, B. Rubi, D. Sebastian, D. Serra, G. Asins, P. Maechler, M. Prentki, and F. G. Hegardt Alteration of the Malonyl-CoA/Carnitine Palmitoyltransferase I Interaction in the {beta}-Cell Impairs Glucose-Induced Insulin Secretion Diabetes, February 1, 2005; 54(2): 462 - 471. [Abstract] [Full Text] [PDF]

				S. C. Gunawardana, Y.-J. Liu, M. J. MacDonald, S. G. Straub, and G. W. G. Sharp Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E828 - E833. [Abstract] [Full Text] [PDF]

				R. Roduit, C. Nolan, C. Alarcon, P. Moore, A. Barbeau, V. Delghingaro-Augusto, E. Przybykowski, J. Morin, F. Masse, B. Massie, et al. A Role for the Malonyl-CoA/Long-Chain Acyl-CoA Pathway of Lipid Signaling in the Regulation of Insulin Secretion in Response to Both Fuel and Nonfuel Stimuli Diabetes, April 1, 2004; 53(4): 1007 - 1019. [Abstract] [Full Text] [PDF]

				S. Yamada, M. Komatsu, Y. Sato, K. Yamauchi, T. Aizawa, and I. Kojima Nutrient Modulation of Palmitoylated 24-Kilodalton Protein in Rat Pancreatic Islets Endocrinology, December 1, 2003; 144(12): 5232 - 5241. [Abstract] [Full Text] [PDF]

				C. Alarcon, B. Wicksteed, M. Prentki, B. E. Corkey, and C. J. Rhodes Succinate Is a Preferential Metabolic Stimulus-Coupling Signal for Glucose-Induced Proinsulin Biosynthesis Translation Diabetes, August 1, 2002; 51(8): 2496 - 2504. [Abstract] [Full Text] [PDF]

				R. Roduit, P. Masiello, S. P. Wang, H. Li, G. A. Mitchell, and M. Prentki A Role for Hormone-Sensitive Lipase in Glucose-Stimulated Insulin Secretion: A Study in Hormone-Sensitive Lipase-Deficient Mice Diabetes, September 1, 2001; 50(9): 1970 - 1975. [Abstract] [Full Text] [PDF]

				J. T. Deeney, J. Gromada, M. Hoy, H. L. Olsen, C. J. Rhodes, M. Prentki, P.-O. Berggren, and B. E. Corkey Acute Stimulation with Long Chain Acyl-CoA Enhances Exocytosis in Insulin-secreting Cells (HIT T-15 and NMRI beta -Cells) J. Biol. Chem., March 24, 2000; 275(13): 9363 - 9368. [Abstract] [Full Text] [PDF]

				B. E. Corkey, J. T. Deeney, G. C. Yaney, K. Tornheim, and M. Prentki The Role of Long-Chain Fatty Acyl-CoA Esters in {beta}-Cell Signal Transduction J. Nutr., February 1, 2000; 130(2): 299 - 299. [Abstract] [Full Text]

				W. W. Winder and D. G. Hardie AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E1 - E10. [Abstract] [Full Text] [PDF]

				H. J. Kennedy, A. E. Pouli, E. K. Ainscow, L. S. Jouaville, R. Rizzuto, and G. A. Rutter Glucose Generates Sub-plasma Membrane ATP Microdomains in Single Islet beta -Cells. POTENTIAL ROLE FOR STRATEGICALLY LOCATED MITOCHONDRIA J. Biol. Chem., May 7, 1999; 274(19): 13281 - 13291. [Abstract] [Full Text] [PDF]

				P. A. Antinozzi, L. Segall, M. Prentki, J. D. McGarry, and C. B. Newgard Molecular or Pharmacologic Perturbation of the Link between Glucose and Lipid Metabolism Is without Effect on Glucose-stimulated Insulin Secretion. A RE-EVALUATION OF THE LONG-CHAIN ACYL-CoA HYPOTHESIS J. Biol. Chem., June 26, 1998; 273(26): 16146 - 16154. [Abstract] [Full Text] [PDF]