全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2009 

Glucagon-Like Peptide-1 Induced Signaling and Insulin Secretion Do Not Drive Fuel and Energy Metabolism in Primary Rodent Pancreatic β-Cells

DOI: 10.1371/journal.pone.0006221

Full-Text   Cite this paper   Add to My Lib

Abstract:

Background Glucagon like peptide-1 (GLP-1) and its analogue exendin-4 (Ex-4) enhance glucose stimulated insulin secretion (GSIS) and activate various signaling pathways in pancreatic β-cells, in particular cAMP, Ca2+ and protein kinase-B (PKB/Akt). In many cells these signals activate intermediary metabolism. However, it is not clear whether the acute amplification of GSIS by GLP-1 involves in part metabolic alterations and the production of metabolic coupling factors. Methodology/Prinicipal Findings GLP-1 or Ex-4 at high glucose caused release (~20%) of the total rat islet insulin content over 1 h. While both GLP-1 and Ex-4 markedly potentiated GSIS in isolated rat and mouse islets, neither had an effect on β-cell fuel and energy metabolism over a 5 min to 3 h time period. GLP-1 activated PKB without changing glucose usage and oxidation, fatty acid oxidation, lipolysis or esterification into various lipids in rat islets. Ex-4 caused a rise in [Ca2+]i and cAMP but did not enhance energy utilization, as neither oxygen consumption nor mitochondrial ATP levels were altered. Conclusions/Significance The results indicate that GLP-1 barely affects β-cell intermediary metabolism and that metabolic signaling does not significantly contribute to GLP-1 potentiation of GSIS. The data also indicate that insulin secretion is a minor energy consuming process in the β-cell, and that the β-cell is different from most cell types in that its metabolic activation appears to be primarily governed by a “push” (fuel substrate driven) process, rather than a “pull” mechanism secondary to enhanced insulin release as well as to Ca2+, cAMP and PKB signaling.

References

[1]  Prentki M (1996) New insights into pancreatic beta-cell metabolic signaling in insulin secretion. Eur J Endocrinol 134: 272–286.
[2]  Prentki M, Joly E, El-Assaad W, Roduit R (2002) Malonyl-CoA Signaling, Lipid Partitioning, and Glucolipotoxicity: Role in beta-Cell Adaptation and Failure in the Etiology of Diabetes. Diabetes 51: Suppl 3S405–413.
[3]  Wiederkehr A, Wollheim CB (2008) Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell. Cell Calcium 44: 64–76.
[4]  Nolan CJ, Prentki M (2008) The islet beta-cell: fuel responsive and vulnerable. Trends Endocrinol Metab 19: 285–291.
[5]  Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M (2006) Fatty Acid Signaling in the {beta}-Cell and Insulin Secretion. Diabetes 55: Suppl 2S16–23.
[6]  Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116: 1802–1812.
[7]  Corkey BE, Glennon MC, Chen KS, Deeney JT, Matschinsky FM, et al. (1989) A role for malonyl-CoA in glucose-stimulated insulin secretion from clonal pancreatic beta-cells. J Biol Chem 264: 21608–21612.
[8]  Wolf BA, Easom RA, McDaniel ML, Turk J (1990) Diacylglycerol synthesis de novo from glucose by pancreatic islets isolated from rats and humans. J Clin Invest 85: 482–490.
[9]  Berne C (1975) The metabolism of lipids in mouse pancreatic islets. The biosynthesis of triacylglycerols and phospholipids. Biochem J 152: 667–673.
[10]  Drucker DJ (2006) The biology of incretin hormones. Cell Metab 3: 153–165.
[11]  Hansotia T, Drucker DJ (2005) GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Regul Pept 128: 125–134.
[12]  Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, et al. (1993) Glucagon-like peptide-1 (7-36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol 138: 159–166.
[13]  Girard J (2008) The incretins: From the concept to their use in the treatment of type 2 diabetes. Part A: Incretins: Concept and physiological functions. Diabetes Metab 34: 550–559.
[14]  Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF (1987) Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A 84: 3434–3438.
[15]  Buteau J, Foisy S, Rhodes CJ, Carpenter L, Biden TJ, et al. (2001) Protein kinase Czeta activation mediates glucagon-like peptide-1-induced pancreatic beta-cell proliferation. Diabetes 50: 2237–2243.
[16]  Mentlein R, Gallwitz B, Schmidt WE (1993) Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 214: 829–835.
[17]  Buteau J, Foisy S, Joly E, Prentki M (2003) Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. Diabetes 52: 124–132.
[18]  Dillon JS, Lu M, Bowen S, Homan LL (2005) The recombinant rat glucagon-like peptide-1 receptor, expressed in an alpha-cell line, is coupled to adenylyl cyclase activation and intracellular calcium release. Exp Clin Endocrinol Diabetes 113: 182–189.
[19]  Holz GG (2004) New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells. Horm Metab Res 36: 787–794.
[20]  Holz GG (2004) Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 53: 5–13.
[21]  Holz GG, Heart E, Leech CA (2008) Synchronizing Ca2+ and cAMP oscillations in pancreatic beta-cells: a role for glucose metabolism and GLP-1 receptors? Focus on “regulation of cAMP dynamics by Ca2+ and G protein-coupled receptors in the pancreatic beta-cell: a computational approach”. Am J Physiol Cell Physiol 294: C4–6.
[22]  McCormack JG, Halestrap AP, Denton RM (1990) Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 70: 391–425.
[23]  Antinozzi PA, Ishihara H, Newgard CB, Wollheim CB (2002) Mitochondrial metabolism sets the maximal limit of fuel-stimulated insulin secretion in a model pancreatic beta cell: a survey of four fuel secretagogues. J Biol Chem 277: 11746–11755.
[24]  Marynissen G, Leclercq-Meyer V, Sener A, Malaisse WJ (1990) Perturbation of pancreatic islet function in glucose-infused rats. Metabolism 39: 87–95.
[25]  Roche E, Assimacopoulos-Jeannet F, Witters LA, Perruchoud B, Corkey BE, et al. (1997) Induction by glucose of genes coding for glycolytic enzymes in a pancreatic β-cell line (INS-1). J Biol Chem 272: 3091–3098.
[26]  Zhang TM, Maggetto C, Malaisse WJ (1994) Hexose metabolism in pancreatic islets: glycogen synthase and glycogen phosphorylase activities. Biochem Med Metab Biol 51: 129–139.
[27]  Buteau J, El-Assaad W, Rhodes CJ, Rosenberg L, Joly E, et al. (2004) Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia 47: 806–815.
[28]  Li L, El-Kholy W, Rhodes CJ, Brubaker PL (2005) Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B. Diabetologia 48: 1339–1349.
[29]  Park S, Dong X, Fisher TL, Dunn S, Omer AK, et al. (2006) Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J Biol Chem 281: 1159–1168.
[30]  Ishiki M, Klip A (2005) Minireview: recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Endocrinology 146: 5071–5078.
[31]  Cazzolli R, Carpenter L, Biden TJ, Schmitz-Peiffer C (2001) A role for protein phosphatase 2A-like activity, but not atypical protein kinase Czeta, in the inhibition of protein kinase B/Akt and glycogen synthesis by palmitate. Diabetes 50: 2210–2218.
[32]  Moule SK, Welsh GI, Edgell NJ, Foulstone EJ, Proud CG, et al. (1997) Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells. Activation of protein kinase B by wortmannin-sensitive and -insensitive mechanisms. J Biol Chem 272: 7713–7719.
[33]  Hahn-Windgassen A, Nogueira V, Chen CC, Skeen JE, Sonenberg N, et al. (2005) Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem 280: 32081–32089.
[34]  da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, et al. (2003) Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression. Biochem J 371: 761–774.
[35]  Prentki M, Madiraju SR (2008) Glycerolipid metabolism and signaling in health and disease. Endocr Rev 29: 647–676.
[36]  Watt MJ, Holmes AG, Pinnamaneni SK, Garnham AP, Steinberg GR, et al. (2006) Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 290: E500–508.
[37]  Peyot ML, Nolan CJ, Soni K, Joly E, Lussier R, et al. (2004) 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 53: 1733–1742.
[38]  Nolan CJ, Leahy JL, Delghingaro-Augusto V, Moibi J, Soni K, et al. (2006) Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia 49: 2120–2130.
[39]  Cunningham BA, Richard AM, Dillon JS, Daley JT, Civelek VN, et al. (2003) Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets. Biochem J 369: 173–178.
[40]  Yaney GC, Civelek VN, Richard AM, Dillon JS, Deeney JT, et al. (2001) Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic beta- cells (HIT).[In Process Citation]. Diabetes 50: 56–62.
[41]  Gotoh M, Maki T, Satomi S, Porter J, Bonner-Weir S, et al. (1987) Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection. Transplantation 43: 725–730.
[42]  Heart E, Smith PJ (2007) Rhythm of the beta-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior. Am J Physiol Endocrinol Metab 292: E1295–1300.
[43]  Massa ML, Borelli MI, Del Zotto H, Gagliardino JJ (2001) Changes induced by sucrose administration on glucose metabolism in pancreatic islets in normal hamsters. J Endocrinol 171: 551–556.
[44]  Kang G, Chepurny OG, Rindler MJ, Collis L, Chepurny Z, et al. (2005) A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells. J Physiol 566: 173–188.
[45]  Chepurny OG, Holz GG (2007) A novel cyclic adenosine monophosphate responsive luciferase reporter incorporating a nonpalindromic cyclic adenosine monophosphate response element provides optimal performance for use in G protein coupled receptor drug discovery efforts. J Biomol Screen 12: 740–746.
[46]  Osbourn DM, Sanger RH, Smith PJ (2005) Determination of single-cell oxygen consumption with impedance feedback for control of sample-probe separation. Anal Chem 77: 6999–7004.
[47]  Jouaville LS, Pinton P, Bastianutto C, Rutter GA, Rizzuto R (1999) Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc Natl Acad Sci U S A 96: 13807–13812.
[48]  Ainscow EK, Rutter GA (2002) Glucose-stimulated oscillations in free cytosolic ATP concentration imaged in single islet beta-cells: evidence for a Ca2+-dependent mechanism. Diabetes 51: Suppl 1S162–170.
[49]  Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129: 1261–1274.
[50]  Liu Z, Habener JF (2008) Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem 283: 8723–8735.
[51]  Widenmaier SB, Sampaio AV, Underhill TM, McIntosh CH (2009) Non-canonical activation of Akt/PKB in beta -cells by the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). J Biol Chem 284: 10764–10773.
[52]  Tsuboi T, da Silva Xavier G, Holz GG, Jouaville LS, Thomas AP, et al. (2003) Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells. Biochem J 369: 287–299.
[53]  Roduit R, Nolan C, Alarcon C, Moore P, Barbeau A, et al. (2004) 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 53: 1007–1019.
[54]  Herrero L, Rubi B, Sebastian D, Serra D, Asins G, et al. (2005) Alteration of the malonyl-CoA/carnitine palmitoyltransferase I interaction in the beta-cell impairs glucose-induced insulin secretion. Diabetes 54: 462–471.
[55]  Maechler P (2002) Mitochondria as the conductor of metabolic signals for insulin exocytosis in pancreatic beta-cells. Cell Mol Life Sci 59: 1803–1818.
[56]  Mulder H, Yang S, Winzell MS, Holm C, Ahren B (2004) Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion. Diabetes 53: 122–128.
[57]  Sorhede Winzell M, Ahren B (2004) Glucagon-like peptide-1 and islet lipolysis. Horm Metab Res 36: 795–803.
[58]  Richards SK, Parton LE, Leclerc I, Rutter GA, Smith RM (2005) Over-expression of AMP-activated protein kinase impairs pancreatic {beta}-cell function in vivo. J Endocrinol 187: 225–235.
[59]  Straub SG, Sharp GW (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 18: 451–463.
[60]  Malsam J, Kreye S, Sollner TH (2008) Membrane fusion: SNAREs and regulation. Cell Mol Life Sci 65: 2814–2832.
[61]  Li F, Pincet F, Perez E, Eng WS, Melia TJ, et al. (2007) Energetics and dynamics of SNAREpin folding across lipid bilayers. Nat Struct Mol Biol 14: 890–896.
[62]  Matschinsky FM (1996) A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 45: 223–241.
[63]  Sener A, Rasschaert J, Malaisse WJ (1990) Hexose metabolism in pancreatic islets. Participation of Ca2(+)-sensitive 2-ketoglutarate dehydrogenase in the regulation of mitochondrial function. Biochim Biophys Acta 1019: 42–50.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133