Skip to main content
SpringerLink
Log in

The Metabolic Basis of Insulin Secretion

  • Chapter
Type 1 Diabetes

Part of the book series: Contemporary Endocrinology ((COE))

  • 620 Accesses

Abstract

All vertebrates use insulin-producing pancreatic β-cells to achieve fuel homeostasis (1). These cells are able to measure the nutrient levels of the blood on a moment-tomoment basis and secrete insulin at rates that are exactly appropriate for the maintenance of optimal fuel levels. Therefore, the levels of circulating nutrients such as glucose, fatty acids, and amino acids are precisely controlled in mammals during fasting and feeding alike. The role of the pancreatic β-cells in fuel homeostasis is thus analogous to that of the thermostat in heating and cooling systems (2,3).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Epple A, Brinn JE. The Comparative Physiology of the Pancreatic Islets. Springer-Verlag, Berlin, 1987.

    Book  Google Scholar 

  2. Matschinsky FM, Collins HW. Essential biochemical design features of the fuel-sensing system in pancreatic β-cells. Chem Biol 1997;4:249–257.

    Article  PubMed  CAS  Google Scholar 

  3. Matschinsky FM. Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 1996;45:223–241.

    Google Scholar 

  4. Newgard CB, Matschinsky FM. Substrate control of insulin release. In: Jefferson L, Cherrington A, eds. Handbook of Physiology. Oxford University Press, Oxford 2001, Vol. 2, pp. 125–151.

    Google Scholar 

  5. Matschinsky FM, Sweet IR. Annotated questions and answers about glucose metabolism and insulin secretion of β3-cells. Diabetes Rev 1996;4:130–144.

    Google Scholar 

  6. Liang Y, Matschinsky FM. Mechanism of action on non glucose insulin secretagogues. Am Rev Nutr 1994;14:59–81.

    Article  CAS  Google Scholar 

  7. Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, et al. Molecular biology of mammalian glucose transporters. Diabetes Care 1990;13:198–208.

    Article  PubMed  CAS  Google Scholar 

  8. Thorens B, Sarkar HK, Kaback HR, Lodish HF. Cloning and functional expression in bacteria of a novel glucose transporter in liver, intestine, kidney and beta-pancreatic islet cells. Cell 1988;55:281–290.

    Article  PubMed  CAS  Google Scholar 

  9. Johnson JH, Newgard CB, Milburn JL, Lodish HF, Thorens B. The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence. J Biol Chem 1990;265:6548–6551.

    PubMed  CAS  Google Scholar 

  10. DeVos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, et al. Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest 1995;96:2489–2495.

    Article  CAS  Google Scholar 

  11. Ferrer J, Benito C, Gomis R. Pancreatic islet GLUT-2 glucose transporter mRNA and protein expression in humans with and without NIDDM. Diabetes 1995;44:1369–1374.

    Article  PubMed  CAS  Google Scholar 

  12. Meglasson MD, Matschinsky FM. Pancreatic islet glucose metabolism and regulation of insulin secretion. Diabetes Metab Rev 1986;2:163–214.

    Article  PubMed  CAS  Google Scholar 

  13. Wilson JE. Regulation of mammalian hexokinase activity. In: Beitner R, ed. Regulation of Carbohydrate Metabolism. CRC, Boca Raton, FL, 1984, pp. 45–85.

    Google Scholar 

  14. Johnson JH, Ogawa A, Chen L, Orci L, Newgard CB, Alam T, et al. Underexpression of β-cell high Km glucose transport in noninsulin-dependent diabetes. Science 1990;250:546–549.

    Article  PubMed  CAS  Google Scholar 

  15. Froguel PH, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, et al. Familial hyperglycemia due to mutations in glucokinase:definition of a subtype of diabetes mellitus. N Engl J Med 1993;328:697–702.

    Article  PubMed  CAS  Google Scholar 

  16. Perales MA, Sener A, Malaisse WJ. Hexose metabolism in pancreatic islets: the glucose-6-phosphate riddle. Mol Cell Biochem 1991;101:67–71.

    Article  PubMed  CAS  Google Scholar 

  17. Khan AV, Chaudramouli V, Gotenson CG, Ahren B, Schumann WC, Low H, et al. Evidence for presence of glucose cycling in pancreatic islets of the ob/ob mouse. J Biol Chem 1989;264:9732–9733.

    PubMed  CAS  Google Scholar 

  18. Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic β-cells. J Biol Chem 1994;269:4895–4902.

    PubMed  CAS  Google Scholar 

  19. Voet D, Voet JG. Electron transporter and oxidative phosphorylation. In: Voet D, Voet JG, eds. Biochemistry. Wiley, New York, 1990, pp. 528–557.

    Google Scholar 

  20. Nelson DL, Cox MM. Oxidative phosphorylation and photophosphorylation. In: Nelson DL, Cox MM, eds. Lehninger Principles of Biochemistry. Worth Publishers, New York, 2000, pp. 659–715.

    Google Scholar 

  21. Darley-Usmar V, Ragan I, Smith P, Wilson M. The proteins of the mitochondrial inner membrane and their role in mitochondria. In: Darley-Usmar V, Schapira AH, eds. DNA, Proteins and Disease. Portland, Chapel Hill, NC, 1994, pp. 1–25.

    Google Scholar 

  22. Liang Y, Bai G, Doliba N, Buettger C, Wang L, Berner DK, et al. Glucose metabolism and insulin release in mouse βHC9 cells as model for wildtype pancreatic β-cells. Am J Physiol 1996;270:E846–E857.

    PubMed  CAS  Google Scholar 

  23. Berman HK, Newgard CB. Fundamental metabolic differences between hepatoyctes and islet β-cells revealed by glucokinase overexpression. Biochemistry 1998;37:4543–4552.

    Article  PubMed  CAS  Google Scholar 

  24. Prentki M, Matschinsky FM. Ca2+, cAMP and phospholipid-derived messengers in coupling mechanism of insulin secretion. Physiol Rev 1987;67:1185–1248.

    PubMed  CAS  Google Scholar 

  25. McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes. Science 1992;258:766–770.

    Article  PubMed  CAS  Google Scholar 

  26. Prentki M, Corkey BE. Are the β-cell signaling molecules malonyl CoA and cytosolic long chainCoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes 1996;45:273–283.

    Article  PubMed  CAS  Google Scholar 

  27. Newgard CB, McGarry JD. Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem 1995;64:689–719.

    Article  PubMed  CAS  Google Scholar 

  28. Corkey BE, Glennon MC, Chen KS, Deeney JT, Matschinsky FM, Prentki M. A role for malonylCoA in glucose-stimulated insulin secretion from clonal pancreatic β3-cells. J Biol Chem 1989;264:21,608–21,612.

    Google Scholar 

  29. Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem 1992;267:5802–5810.

    PubMed  CAS  Google Scholar 

  30. McGarry JD, Woeltje KF, Kuwajima M, Foster DW. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab Rev 1989;5:271–284.

    Article  PubMed  CAS  Google Scholar 

  31. Chen S, Ogawa A, Ohneda M, Unger RH, Foster DW, McGarry JD. More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic β-cell signalling. Diabetes 1994;43:878–883.

    Article  PubMed  CAS  Google Scholar 

  32. Cook DL, Hales N. Intracellular ATP directly blocks K+-channels in pancreatic β-cells. Nature 1984;311:269–271.

    Article  PubMed  CAS  Google Scholar 

  33. Ashcroft FM, Harrison DE, Aschroft SHJ. Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 1984;312:446–448.

    Article  PubMed  CAS  Google Scholar 

  34. Misler S, Falke LC, Gillis K, McDaniel ML. A metabolite-regulated potassium channel in rat pancreatic B cells. Proc Natl Acad Sci USA 1986;83:7119–7123.

    Article  PubMed  CAS  Google Scholar 

  35. Atwater I, Mears D, Rojas E. Electrophysiology of the pancreatic β-cell, In: Leroith D, Taylor SI, Olefsky JM, eds. Diabetes Mellitus (A Fundamental and Clinical Text). Lippincott-Raven, New York, 1996, pp. 78–102.

    Google Scholar 

  36. Misler S, Pressel DM, Barnett DW. Stimulus transduction in metabolic sensor cells. In: Speralakis N, ed. Cell Physiology Source Book. Academic, San Diego, CA, 1998, pp. 652–667.

    Google Scholar 

  37. Gembal M, Detimary P, Gilon P, Gao Z-Y, Henquin JC. Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K channels in mouse β-cells. J Clin Invest 1993;91:871–880.

    Article  PubMed  CAS  Google Scholar 

  38. Ganesan S, Calle R, Zawalich K, Greenawalt K, Zawalich W, Rasmussen H. Immunocytochemical location of a-protein kinase C in rat pancreatic β-cells during glucose-induced insulin secretion. J Cell Biol 1992;119:313–324.

    Article  PubMed  CAS  Google Scholar 

  39. Calle R, Ganesan S, Smallwood JI, Rasmussen H. Glucose-induced phosphorylation of myristolated alanine-rich C kinase substrate (MARCKS) in isolated rat pancreatic islets. J Biol Chem 1992;267:18,723–18,727.

    CAS  Google Scholar 

  40. Prentki M, Glennon MC, Geschwind J-F, Matschinsky FM, Corkey BE. Cyclic AMP raises cytosolic Ca2+ and promotes Ca2+ influx in a clonal pancreatic β-cell line (HIT T-15). FEBS Lett 1987;220(1):103–107.

    Article  PubMed  CAS  Google Scholar 

  41. Albano JDM, Barnes GD. Factors affecting the saturation assay of cyclic AMP in biological systems. Anal Biochem 1974;60:130–141.

    Article  PubMed  CAS  Google Scholar 

  42. Hutton JC, Malaisse WJ. Dynamics of 02 consumption in rat pancreatic islets. Diabetologia 1980;18:395–405.

    PubMed  CAS  Google Scholar 

  43. Hopkins WF, Fatherazi S, Peter-Riesch B, Corkey BE, Cook DL. Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic beta-cells and HIT cells. J Membr Biol 1992;129:287–295.

    PubMed  CAS  Google Scholar 

  44. Balasse EO, Ooms HA. Role of plasma free acids in the control of insulin secretion in man. Diabetologia 1973;9:145–151.

    Article  PubMed  CAS  Google Scholar 

  45. Liang Y, Matschinsky FM. Content of CoA-esters in perifused rat islets stimulated by glucose and other fuels. Diabetes 1991;40:327–333.

    Article  PubMed  CAS  Google Scholar 

  46. Vara E, Tamarit-Rodriguez J. Effects of L-leucine on palmitate metabolism and insulin release by isolated islets of fed and starved rats. Endocrinology 1986;119:404–407.

    Article  PubMed  CAS  Google Scholar 

  47. Vara E, Tamarit-Rodriguez J. Glucose stimulation of insulin secretion in islets of fed and starved rats and its dependence on lipid metabolism. Metabolism 1986;35:266–271.

    Article  PubMed  CAS  Google Scholar 

  48. Tamarit-Rodriguez J, Vara E, Tamarit J. Starvation-induced secretory changes of insulin, somatostatin, and glucagon and their modification by 2-bromostearate. Horm Metab Res 1984;16:115–119.

    Article  PubMed  CAS  Google Scholar 

  49. Tamarit-Rodriguez J, Vara E, Tamarit J. Starvation-induced changes of palmitate metabolism and insulin secretion in isolated rat islets stimulated by glucose. Biochem J 1984;221:317–324.

    PubMed  CAS  Google Scholar 

  50. Bedoya FJ, Ramirez R, Arilla E, Goberna R. Effect of 2-bromostearate on glucose-phosphorylating activities and the dynamics of insulin secretion in islets of Langerhans during fasting. Diabetes 1984;33:858–863.

    Article  PubMed  CAS  Google Scholar 

  51. Stein DT, Esser V, Stevenson BE, Lane KE, Whiteside JH, Daniels MB, et al. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 1996;97:2728–2735.

    Article  PubMed  CAS  Google Scholar 

  52. Stein DT, Stevenson BE, Chester MW, Basit M, Daniels MB, Turley SD, et al. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest 1997;100:398–403.

    Article  PubMed  CAS  Google Scholar 

  53. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications. Diabetes 1995;44:863–870.

    Article  PubMed  CAS  Google Scholar 

  54. Katahira H, Nagamatsu S, Ozawa S, Nakamichi Y, Yamaquchi S, Furukawa H, et al. Acute inhibition of proinsulin biosynthesis at the translational level by palmitic acid. Biochem Biophys Res Commun 2001;282(2):507–510.

    Article  PubMed  CAS  Google Scholar 

  55. Chan CB, De Leo D, Joseph JW, McQuaid TS, Ha XF, Xu F, et al. Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 2001;50(6):1302–1310.

    Article  PubMed  CAS  Google Scholar 

  56. Antinozzi P, Prentki M, Segall L, McGarry JD, Newgard CB. 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 1998;273(26):16,146–16,154.

    Article  CAS  Google Scholar 

  57. Chen G, Koyama K, Ynan X, Lee Y, Zhou YT, O’Doherty R, et al. Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proc Natl Acad Sci USA 1996;93:14,795–14,799.

    Google Scholar 

  58. Dobbins RL, Chester MW, Daniels MB, McGarry JD, Stein DT. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. Diabetes 1998;47(10):1613–1618.

    Article  PubMed  CAS  Google Scholar 

  59. Sugden MC, Bulmer K, Holness MJ. Fuel-sensing mechanisms integrating lipid and carbohydrate utilization. Biochem Soc Trans 2001;29:272–278.

    Article  PubMed  CAS  Google Scholar 

  60. Wahren J, Felig P. Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus. J Clin Invest 1976;57:987–999.

    Article  PubMed  CAS  Google Scholar 

  61. Fajans S, Floyd JL, Knopf RF, Conn JW. Effects of amino acids and proteins on insulin secretion in man. Recent Prog Horm Res 1967;23:617–656.

    PubMed  CAS  Google Scholar 

  62. Felig Ph. Amino acid metabolism in man. Annu Rev Biochem 1975;44:933–955.

    Article  PubMed  CAS  Google Scholar 

  63. DeFronzo RA, Felig Ph. Amino acids in uremia: insight gained from normal and diabetic man. Am J Clin Nutr 1980:33:1378–1386.

    PubMed  CAS  Google Scholar 

  64. Pagliara AS, Stillings SN, Hover BA, Martin DM, Matschinsky FM. Glucose modulation of amino acid induced glucagon and insulin release in the isolated perfused rat pancreas. J Clin Invest 1974;54:819–832.

    Article  PubMed  CAS  Google Scholar 

  65. Braunstein AE, Bychkov SM. A cell-free enzymic model of 1-amino-acid dehydrogenase (1´ deaminase). Nature 1939;144:751–752.

    Article  Google Scholar 

  66. Matschinsky FM, Fertel R, Kotler-Brajtburg J, Stillings S, Ellerman J, Raybaud F, et al. Factors governing the action of small calorigenic molecules on the islets of Langerhans. In: Mussacchia XJ, Breitenbach RP, eds. 8th Midwest Conference on Endocrinology and Metabolism. University of Missouri-Columbia Press, Columbia, 1973, pp. 63–87.

    Google Scholar 

  67. Matschinsky FM, Ellerman J, Stillings S, Raybaud F, Pace C, Zawalich W. Hexoses and insulin secretion. In: Hasselblatt A, Bruchhausen FV, eds. Handbook of Experimental Pharmacology, New Series. Springer-Verlag, Berlin, 1975, pp. 79–114.

    Google Scholar 

  68. Sener A, Malaisse WJ. The stimulus secretion coupling of amino acids induced insulin release: insulinotropic action of branched-chained amino acids at physiological concentrations of glucose and glutamine. Eur J Clin Invest 1981;11:455–460.

    Article  PubMed  CAS  Google Scholar 

  69. Sener A, Malaisse-Lagae F, Malaisse WJ. Stimulation of pancreatic ilset metabolism and insulin release by a non metabolizable amino acid. Proc Natl Acad Sci USA 1981;78:5460–5464.

    Article  PubMed  CAS  Google Scholar 

  70. Panten U, Zielmann S, Langer J, Zunkler BJ, Lenzen S. Regulation of insulin secretion by energy metabolism in pancreatic β-cell mitochondria. Studies with a non-metabolizable leucine analogue. Biochem J 1984;219:189–196.

    PubMed  CAS  Google Scholar 

  71. Malaisse-Lagae F, Sener A, Garcia-Morales P, Valverde I, Malaisse WJ. The stimulus-secretion coupling of amino acid-induced insulin release. Influence of a nonmetabolized analog of leucine on the metabolism of glutamine in pancreatic islets. J Biol Chem 1982;257:3754–3758.

    PubMed  CAS  Google Scholar 

  72. Malaisse WJ, Carpinelli AR, Lebrun P, Herchulz A, Sener A. The stimulus-secretion coupling of amino acid-induced insulin release. IV. Ionic response to L-leucine and L-glutamine. Pflugers Arch 1981;391:112–118.

    Article  PubMed  CAS  Google Scholar 

  73. Malaisse WJ, Hutton JC, Carpinelli AR, Herchuelz A, Sener A. The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. Diabetes 1980;29:431–437.

    Article  PubMed  CAS  Google Scholar 

  74. Malaisse WJ, Sener A, Malaisse-Lagae F, Welsh M, Matthews DE, Bier DM, et al. The stimulus-secretion coupling of amino acid-induced insulin release. Metabolic response of pancreatic islets of L-glutamine and L-leucine. J Biol Chem 1982;257:8731–8737.

    PubMed  CAS  Google Scholar 

  75. Sener A, Malaisse-Lagae F, Malaisse WJ. The stimulus-secretion coupling amino acid-induced insulin release. XII. Contrasting effects of L-leucine and a nonmetabolized analog upon islet metabolism and insulin secretion. Horm Metab Res 1982:14:459–463.

    Article  PubMed  CAS  Google Scholar 

  76. Gao Z, Li G, Najafi H, Wolf BA, Matschinsky FM. Glucose regulation of glutaminolysis and its role in insulin secretion. Diabetes 1999;47:1535–1542.

    Article  Google Scholar 

  77. Hudson RC, Daniel RM. Glutamate dehydrogenase: distribution, properties, and mechanism. Exp Biochem Physiol 1993;106B:767–792.

    CAS  Google Scholar 

  78. Bryla J, Michalek M, Nelson J, Erecinska M. Regulation of glutamate dehydrogenase activity in rat islets of Langerhans and its consequences on insulin release. Metabolism 1994;43:1187–1195.

    Article  PubMed  CAS  Google Scholar 

  79. Weinzimer SA, Stanley CA, Berry GT, Yudkoff M, Tuchman M, Thornton PS. A syndrome of congenital hyperinsulinism and hyperammonemia. J Pediatr 1997;130:661–664.

    Article  PubMed  CAS  Google Scholar 

  80. Stanley CA, Lien KY, Hsu BYL, Burlina AB, Greenberg CR, Hopwood NJ, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutation of glutamate dehydrogenase. N Engl J Med 1998;338(19): 1352–1357.

    Article  PubMed  CAS  Google Scholar 

  81. Michalik M, Nelson J, Erecinska M. Glutamate production in islets of Langerhans: properties of phosphate-activated glutaminase. Metabolism 1992;41:1319–1326.

    Article  PubMed  CAS  Google Scholar 

  82. Curthoys NP. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 1995;15:133–159.

    Article  PubMed  CAS  Google Scholar 

  83. Low SY, Salter M, Knowles RG, Pogson CI, Rennie MJ. A quantitative analysis of the control of glutamine catabolism in rat liver cells. Use of selective inhibitors. Biochem J 1993;295:617–624.

    PubMed  CAS  Google Scholar 

  84. Lenzen S, Schmidt W, Rustenbeck I, Panten U. 2-Ketoglutarate generation in pancreatic β-cell mitochondria regulates insulin secretory action of amino acids and 2-ketoacids. Biosci Rep 1986;6:163–169.

    Article  PubMed  CAS  Google Scholar 

  85. Knopf RF, Fajans SS, Floyd JG Jr, Conn JW. Comparison of experimentally induced and naturally occurring sensitivity to leucine hypoglycemia. J Clin Endocrinol Metab 1963;23:579.

    Article  PubMed  CAS  Google Scholar 

  86. MacDonald MJ, Fahien LA, McKenzie DI, Moran SM. Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets. Am J Physiol (Endocr Metab 22) 1990;259:E548-E554.

    CAS  Google Scholar 

  87. MacDonald MJ, McKenzie DI, Kaysen JH, Walker TM, Moran SM, Fahien LA, et al. Glucose regulates leucine-induced insulin release and the expression of the branched chain ketoacid dehydrogenase El alpha subunit gene in pancreatic islets. J Biol Chem 1991;266:1335–1340.

    PubMed  CAS  Google Scholar 

  88. Siegel EG, Wollheim CB, Janjic D, Ribes G, Sharp GW. Involvement of Ca2+ in the impaired glucose-induced insulin release from islets cultured at low glucose. Diabetes 1983;32:993–1000.

    Article  PubMed  CAS  Google Scholar 

  89. Hellerstrom C. Effects of carbohydrates on oxygen consumption of isolated pancreatic islets of mice. Endocrinology 1967;81:105–112.

    Article  PubMed  CAS  Google Scholar 

  90. Aleyassine H. Energy requirements for insulin release from rat pancreas in vivo. Endocrinology 1970;87:84–89.

    Article  PubMed  CAS  Google Scholar 

  91. Lenzen S. Effects of a-ketocarboxylic acids and 4-pentenoic acid on insulin secretion from the perfused rat pancreas. Biochem Pharmacol 1979;27:1321–1324.

    Article  Google Scholar 

  92. Sener A, Kawazu S, Hutton JC, Boschero AC, Devis G, Somers G, et al. The stimulus secretion coupling of glucose-induced insulin release. Biochem J 1978;176:217–232.

    PubMed  CAS  Google Scholar 

  93. Dukes ID, McIntyre MS, Mertz RJ, Philipson LH, Roe MW, Spencer B, et al. Dependence on NADH produced during glycolysis for beta-cell glucose signaling. 3rd. J Biol Chem 1994;269(15): 10,979–10,982.

    CAS  Google Scholar 

  94. MacDonald MJ. High content of mitochondrial glycerol-3-phosphate dehydrogenase in pancreatic islets and its inhibition by diazoxide. J Biol Chem 1981;256(16):8287–8290.

    PubMed  CAS  Google Scholar 

  95. MacDonald MJ. Evidence for the malate aspartate shuttle in pancreatic islets. Arch Biochem Biophys 1982;213(2):643–649.

    Article  PubMed  CAS  Google Scholar 

  96. Maechler P, Kennedy ED, Pozzan T, Wollheim CB. Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic β-cells. EMBO J 1997;16:3833–3841.

    Article  PubMed  CAS  Google Scholar 

  97. Kennedy ED, Rizzalo R, Theler JM, Pralong WF, Bastianutto C, Pozzan T, et al. Glucose stimulated insulin secretion correlates with changes in mitochondrial and cytosolic Ca2+ in aequorin-expressing INS-1 cells. J Clin Invest 1996;98:2524–2538.

    Article  PubMed  CAS  Google Scholar 

  98. Maechler P, Wollheim CB. Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 1999;402:685–689.

    Article  PubMed  CAS  Google Scholar 

  99. McCormack JG, Longo EA, Corkey BE. Glucose-induced activation of pyruvate dehydrogenase in isolated rat pancreatic islets. Biochem J 1990;267:527–530.

    PubMed  CAS  Google Scholar 

  100. McCormack JG, Halestrap AP, Denton RM. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 1990;70(2):391–425.

    PubMed  CAS  Google Scholar 

  101. Rasschaert J, Malaisse WJ. Hexose metabolism in pancreatic islets. Glucose-induced and Ca2+dependent activation of FAD-glycerophosphate dehydrogenase. Biochem J 1991;278:335–340.

    PubMed  CAS  Google Scholar 

  102. Erecinska M, Bryla J, Michalik M, Meglasson MD, Nelson D. Energy metabolism in islets of Langerhans. Biochem Biophys Acta 1992;1101:273–295.

    Article  PubMed  CAS  Google Scholar 

  103. Eto K, Tsubamoto Y, Terauchi Y, Sugiyama T, Kishimoto T, Takahashi N, et al. Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science 1999;283:981–985.

    Article  PubMed  CAS  Google Scholar 

  104. Gerbitz KD, Gempel K, Brediczka D. Mitochondria and diabetes. Genetic, biochemical and clinical implications of the cellular energy circuit. Diabetes 1996;45:113–126.

    Article  PubMed  CAS  Google Scholar 

  105. Kadowaki T. Maternally inherited diabetes and deafness: new subtype of diabetes mellitus. In: LeRoith D, Taylor SI, Olefsky JM, eds. Diabetes Mellitus, A Fundamental and Clinical Text. Lippincott—Raven, New York, 1996, pp. 591–595.

    Google Scholar 

  106. Mathews CE, McGraw RH, Berdanier CD. A point mutation in the mitochondrial DNA of diabetes prone BHE cdb rats. FASEB J 1995;9:1638–1642.

    PubMed  CAS  Google Scholar 

  107. Liang Y, Bonner-Weir S, Wu YJ, Berdanier CD, Berner DK, Efrat S, et al. In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents. J Clin Invest 1994;93:2473–2481.

    Article  PubMed  CAS  Google Scholar 

  108. Holz GG, Habener JF. Signal transduction cross talk in the endocrine system: pancreatic β-cells and the glucose competency concept. Trends Biochem Sci 1992;17:388–393.

    Article  PubMed  CAS  Google Scholar 

  109. Pralong WF, Bartley C, Wollheim CB. Single islet β-cell stimulation by nutrients: relationship between pyridine nucleotides, cytosolic Ca2+ and secretion. EMBO J 1990;9:53–60.

    PubMed  CAS  Google Scholar 

  110. Meda P. Molecular biology of gap junction proteins. In: Draznin B, LeRoith D, eds. Molecular Biology of Diabetes, Part 1. Humana, Totowa, NJ, 1994, pp. 333–356.

    Chapter  Google Scholar 

  111. Juhl CB, Schmitz O, Pincus S, Holst JJ, Veldhuis J, Porksen N. Short-term treatment with GLP-1 increases pulsatile insulin secretion in type II diabetes with no effect on orderliness. Diabetologia 2000;43(5):583–588.

    Article  PubMed  CAS  Google Scholar 

  112. Doliba N, Vatamaniuk M, Najafi H, Boettger C, Collins H, Grippo J, et al. Novel pharmacological glucokinase activators enhance glucose metabolism, respiration and insulin release in isolated pancreatic islets demonstrating a unique therapeutic potential. Diabetes 2001;50:359A (abstract).

    Google Scholar 

  113. Grimsky J, Sarabu R, Bizzarro F, Coffey J, Chu C, Corbett W, et al. Allosteric activation of islet and hepatic glucokinase: a potential new approach to diabetes therapy. Diabetes 2001;50:115A (abstract).

    Google Scholar 

  114. Cuesta-Munoz A, Boettger C, Davis E, Shiota C, Magnuson M, Grippo J, et al. Novel pharmacological glucokinase activators enhance glucose metabolism, respiration and insulin release in isolated pancreatic islets demonstrating a unique therapeutic potential. Diabetes 2001;50:109A (abstract).

    Google Scholar 

  115. Newgard CB, Clark S, BeltrandelRio H, Hohmeier HE, Quaade C, Normington K. Engineered cell lines for insulin replacement in diabetes: current status and future prospects. Diabetologia 1997;40:S42-S47.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Nicolai M. Doliba PhD, DSci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz M. Matschinsky MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Mark A. Sperling MD (Professor of Pediatrics and Chair Emeritus) (Professor of Pediatrics and Chair Emeritus)

  2. Division of Endocrinology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Mark A. Sperling MD (Professor of Pediatrics and Chair Emeritus) (Professor of Pediatrics and Chair Emeritus)

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Doliba, N.M., Matschinsky, F.M. (2003). The Metabolic Basis of Insulin Secretion. In: Sperling, M.A. (eds) Type 1 Diabetes. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-310-1_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-310-1_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-258-2

  • Online ISBN: 978-1-59259-310-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation