Signaling of insulin secretion by pancreatic β cell. A review
Keywords:
Insulin, MCF, oxidative stressAbstract
Substances such as glucose, free fatty acids and amino acids are metabolized in the β cell when their intracellular concentrations reach certain levels to provide regulatory metabolic coupling factors (R-MCF) and effector (E-FCM). The R-MCF (eg, citrate, NADH/NAD+, malonyl-CoA, GTP, acyl compounds CoA long chain, glutamate, adenine nucleotides), directly or indirectly improve the production of E-MCF (eg, ATP, cAMP, monoacylglycerol, NADPH, ROS, acyl-CoA short-chain compounds), which have a direct impact on the exocytosis of insulin granules. The E-MCF activate the final components of the machinery of exocytosis, including the K+ATP/SUR1/Ca2+, Munc13-1 channel, among others, initiating insulin release. However, in order to prevent excessive secretion of insulin, β cells are also equipped with mechanisms that control excessive production of R-MCF and MCF-E. These mechanisms include metabolic pathways which act as negative modulators (AMPK, palmitoiltransferasa I carnitine, glucose-6-phosphatase, and uncoupling proteins 2, which decreases the generation of R-MCF, and signals controlling the levels of E-MCF. Thus, knowledge of some update signaling pathways involved in insulin secretion is important to better understand the pathogenesis of type 2 diabetes mellitus, where, in addition, oxidative stress plays a significant role. Finally it is considered, an important research area as it can generate new insights into the molecular pathogenesis of hyperglycemia and identify pharmacological targets for treatment and/or prevention of long-term diabetic complications.
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References
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[15] Cline GW, Lepine RL, Papas KK, Kibbey RG, Shulman GI. 13c Nmr isotopomer analysis of anaplerotic pathways in INS-1 cells. J Biol Chem 2004; 279:44370-44375.
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[18] Macdonald MJ, Longacre MJ, Langberg EC, Tibell A, Kendrick MA, Fukao T et al. Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes. Diabetologia 2009; 52:1087-1091.
[19] Maechler P, Li N, Casimir M, Vetterli L, Frigerio F, Brun T. Role of mitochondria in beta-cell function and dysfunction. Adv Exp Med Biol 2010; 654:193-216.
[20] Stanley CA. Two genetic forms of hyperinsulinemic hypoglycemia caused by dysregulation of glutamate dehydrogenase. Neurochem Int 2011; 59:465-472.
[21] Prentki M, Madiraju SR. Glycerolipid metabolism and signaling in health and disease. Endocr Rev 2008; 29:647-676.
[22] Yaney GC, Corkey BE. Fatty acid metabolism and insulin secretion in pancreatic beta cells. Diabetologia 2003; 46:1297-1312.
[23] Herrero L, Rubi B, Sebastian D, Serra D, Asins G, Maechler P et al. Alteration of the malonyl-CoA/carnitine palmitoyltransferase I interaction in the beta-cell impairs glucose-induced insulin secretion. Diabetes 2005; 54:462-471.
[24] Roduit R, Nolan C, Alarcon C, Moore P, Barbeau A, Delghingaro-Augusto V 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 2004; 53:1007-1019.
[25] Antinozzi PA, Segall L, Prentki M, Mcgarry JD, Newgard CB. Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion. J Biol Chem 1998; 273:16146-16154.
[26] Schulze Du, Dufer M, Wieringa B, Krippeit-Drews P, Drews G. An adenylate kinase is involved in KATP channel regulation of mouse pancreatic beta cells. Diabetologia 2007; 50:2126-2134.
[27] Drews G, Krippeit-Drews P, Dufer M. Electrophysiology of islet cells. Adv Exp Med Biol 2010; 654:115-163.
[28] Ruderman N, Prentki M. AMP kinase and malonyl- CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 2004; 3:340-351.
[29] Prentki M, Madiraju SR. Glycerolipid/free fatty acid cycle and islet beta-cell function in health, obesity and diabetes. Mol Cell Endocrinol 2012; 353:88-100.
[30] Lamontagne J, Pepin E, Peyot ML, Joly E, Ruderman NB, Poitout V et al. Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic beta-cell at submaximal glucose concentrations. Endocrinology 2009; 150:3465-3474.
[31] Fu A, Eberhard CE, Screaton RA. Role of AMPK in pancreatic beta cell function. Mol Cell Endocrinol 2013; 366:127-134
[32] Nolan CJ, Leahy JL, Delghingaro-Augusto V, Moibi J, Soni K, Peyot ML et al. Beta-cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia 2006 49:2120-2130.
[33] Peyot ML, Nolan CJ, Soni K, Joly E, Lussier R, Corkey BE et al. Hormone-sensitive lipase has a role in lipid signaling for insulin secretion but is nonessential for the incretin action of glucagon-like peptide 1. Diabetes 2004; 53:1733-1742.
[34] Mulder H, Yang S, Winzell MS, Holm C, Ahren B. Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion. Diabetes 2004; 53:122-128.
[35] Bratanova-Tochkova TK, Cheng H, Daniel S, Gunawardana S, Liu YJ, Mulvaney-Musa J. et al. Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 2002; 51 (Suppl. 1):S83-S90.
[36] Gonzalo S, Linder ME. SNAP-25 palmitoylation and plasma membrane targeting require a functional secretory pathway. Mol Biol Cell 1998; 9:585-597.
[37] Chapman ER, Blasi J, An S, Brose N, Johnston PA, Sudhof TC, Jahn R. Fatty acylation of synaptotagmin in PC12 cells and synaptosomes. Biochem Biophys Res Commun 1996; 225:326-332.
[38] Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell 2002; 108:121-133.
[39] Kwan EP, Xie L, Sheu L, Nolan CJ, Prentki M, Betz A et al. Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose tolerance. Diabetes 2006; 55:1421-1429.
[40] Brownlee M. A radical explanation for glucose-induced beta cell dysfunction. J Clin Invest 2003; 112:1788-1790.
[41] Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St-Pierre J, Grey ST et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 2003; 112:1831-1842.
[42 ]Seino S, Shibasaki T. PKA-dependent and PKAindependent pathways for cAMP-regulated exocytosis. Physiol Rev 2005; 85:1303-1342.
[43] Safayhi H, Haase H, Kramer U. L-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells. Mol Endocrinol 1997; 11:619-629.
[44] Thorens B, Deriaz N, Bosco D. Protein kinase Adependent phosphorylation of GLUT2 in pancreatic β cells. J Biol Chem 1996; 271:8075-8081.
[45] Sugawara K, Shibasaki T, Mizoguchi A, Saito T, Seino S. Rab11 and its effector Rip11 participate in regulation of insulin granule exocytosis. Genes Cells 2009; 14:445-456.
[46] Seino S. Cell signalling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea. Diabetología 2012; 55:2096-2108.
[47] De Rooij J, Rehmann H, Van Triest M, Cool RH, Wittinghofer A, Bos JL. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem 2000; 275:20829-20836.
[48]De Rooij J, Zwartkruis FJ, Verheijen MH. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998; 396:474-477.
[49] Kawasaki H, Springett GM, Mochizuki N. A family of cAMP-binding proteins that directly activate Rap1. Science 1998; 282:2275-2279.
[50] Gloerich M, Bos JL. Epac: defining a new mechanism for cAMP action. Annu Rev Pharmacol Toxicol 2010; 50:355-375.
[51] Li Y, Asuri S, Rebhun JF, Castro AF, Paranavitana NC, Quilliam LA. The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane. J Biol Chem 2006; 281:2506-2514.
[52] Liu C, Takahashi M, Li Y. Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2. Mol Cell Biol 2008; 28:7109-7125.
[53] Niimura M, Miki T, Shibasaki T, Fujimoto W, Iwanaga T, Seino S. Critical role of the N-terminal cyclic AMP-bindingdomain of Epac2 in its subcellular localization and function. J Cell Physiol 2009; 219:652-658.
[54] Shibasaki T, Takahashi H, Miki T. Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci USA 2007; 104:19333-19338.
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Published
2018-05-29
How to Cite
Corro, A., Medina, I., & Matheus, N. (2018). Signaling of insulin secretion by pancreatic β cell. A review. Gaceta De Ciencias Veterinarias, 22(2), 53-62. Retrieved from https://revistas.uclave.org/index.php/gcv/article/view/531
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Section
Review article
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