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Diabetologia

Erschienen in:

01.10.2003 | Review

Fatty acid metabolism and insulin secretion in pancreatic beta cells

verfasst von: G. C. Yaney, Dr. B. E. Corkey

Erschienen in: Diabetologia | Ausgabe 10/2003

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Abstract

Increases in glucose or fatty acids affect metabolism via changes in long-chain acyl-CoA formation and chronically elevated fatty acids increase total cellular CoA. Understanding the response of pancreatic beta cells to increased amounts of fuel and the role that altered insulin secretion plays in the development and maintenance of obesity and Type 2 diabetes is important. Data indicate that the activated form of fatty acids acts as an effector molecule in stimulus-secretion coupling. Glucose increases cytosolic long-chain acyl-CoA because it increases the "switch" compound malonyl-CoA that blocks mitochondrial β-oxidation, thus implementing a shift from fatty acid to glucose oxidation. We present arguments in support of the following: (i) A source of fatty acid either exogenous or endogenous (derived by lipolysis of triglyceride) is necessary to support normal insulin secretion; (ii) a rapid increase of fatty acids potentiates glucose-stimulated secretion by increasing fatty acyl-CoA or complex lipid concentrations that act distally by modulating key enzymes such as protein kinase C or the exocytotic machinery; (iii) a chronic increase of fatty acids enhances basal secretion by the same mechanism, but promotes obesity and a diminished response to stimulatory glucose; (iv) agents which raise cAMP act as incretins, at least in part, by stimulating lipolysis via beta-cell hormone-sensitive lipase activation. Furthermore, increased triglyceride stores can give higher rates of lipolysis and thus influence both basal and stimulated insulin secretion. These points highlight the important roles of NEFA, LC-CoA, and their esterified derivatives in affecting insulin secretion in both normal and pathological states.

Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787CrossRefPubMed

Fraze E, Donner CC, Swislocki AL, Chiou YA, Chen YD, Reaven GM (1985) Ambient plasma free fatty acid concentrations in noninsulin-dependent diabetes mellitus: evidence for insulin resistance. J Clin Endocrinol Metab 61:807–811

Lewis B, Mancini M, Mattock M, Chait A, Fraser TR (1972) Plasma triglyceride and fatty acid metabolism in diabetes mellitus. Eur J Clin Invest 2:445–453PubMed

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

Coleman DL (1978) Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14:141–148PubMed

Porte D Jr (1991) Banting lecture 1990. Beta-cells in type II diabetes mellitus. Diabetes 40:166–180PubMed

Arch JR, Ainsworth AT, Cawthorne MA et al. (1984) Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 309:163–165PubMed

Bloom JD, Dutia MD, Johnson BD et al. (1992) Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent beta-adrenergic agonist virtually specific for β3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem 35:3081–3084PubMed

Holloway BR, Howe R, Rao BS, Stribling D (1992) ICI D7114: a novel selective adrenoceptor agonist of brown fat and thermogenesis. Am J Clin Nutr 55:262S–264SPubMed

10.

Yoshida T (1992) The antidiabetic β3-adrenoceptor agonist BRL 26830A works by release of endogenous insulin. Am J Clin Nutr 55:237S–241SPubMed

11.

Himms-Hagen J, Cui J, Danforth E Jr et al. (1994) Effect of CL-316,243, a thermogenic β3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 266:R1371–R1382PubMed

12.

Susulic VS, Frederich RC, Lawitts J et al. (1995) Targeted disruption of the β3-adrenergic receptor gene. J Biol Chem 270:29483–29492CrossRefPubMed

13.

Grujic D, Susulic VS, Harper ME et al. (1997) β3-adrenergic receptors on white and brown adipocytes mediate beta3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake. A study using transgenic and gene knockout mice. J Biol Chem 272:17686–17693CrossRefPubMed

14.

Hedeskov CJ (1980) Mechanism of glucose-induced insulin secretion. Physiol Rev 60:442–509PubMed

15.

Ashcroft FM, Harrison DE, Ashcroft SJ (1984) Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 312:446–448PubMed

16.

Arkhammar P, Nilsson T, Rorsman P, Berggren PO (1987) Inhibition of ATP-regulated K⁺ channels precedes depolarization-induced increase in cytoplasmic free Ca²⁺ concentration in pancreatic β-cells. J Biol Chem 262:5448–5454PubMed

17.

Prentki M, Matschinsky FM (1987) Ca²⁺, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol Rev 67:1185–1248PubMed

18.

Turk J, Wolf BA, McDaniel ML (1987) The role of phospholipid-derived mediators including arachidonic acid, its metabolites, and inositoltrisphosphate and of intracellular Ca²⁺ in glucose-induced insulin secretion by pancreatic islets. Prog Lipid Res 26:125–181CrossRefPubMed

19.

Corkey BE, Tornheim K, Deeney JT et al. (1988) Linked oscillations of free Ca²⁺ and the ATP/ADP ratio in permeabilized RINm5F insulinoma cells supplemented with a glycolyzing cell-free muscle extract. J Biol Chem 263:4254–4258PubMed

20.

Corkey BE, Deeney JT, Glennon MC, Matschinsky FM, Prentki M (1988) Regulation of steady-state free Ca²⁺ levels by the ATP/ADP ratio and orthophosphate in permeabilized RINm5F insulinoma cells. J Biol Chem 263:4247–4253PubMed

21.

Longo EA, Tornheim K, Deeney JT, Varnum BA, Tillotson D, Prentki M, Corkey BE (1991) Oscillations in cytosolic free Ca²⁺, oxygen consumption, and insulin secretion in glucose-stimulated rat pancreatic islets. J Biol Chem 266:9314–9319PubMed

22.

Malaisse WJ, Malaisse-Lagae F, Sener A (1984) Coupling factors in nutrient-induced insulin release. Experientia 40:1035–1043PubMed

23.

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

24.

Corkey B, Glennon MC, Chen KS, Deeney JT, Matschinsky FM, Prentki M (1989) A role for malonyl-CoA in glucose-stimulated insulin secretion from clonal pancreatic β-cells. J Biol Chem 264:21608–21612PubMed

25.

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

26.

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

27.

Berne C (1975) The metabolism of lipids in mouse pancreatic islets. The biosynthesis of triacylglycerols and phospholipids. Biochem J 152:667–673PubMed

28.

Berne C (1975) The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies. Biochem J 152:661–666PubMed

29.

Vara E, Tamarit-Rodriguez J (1986) Glucose stimulation of insulin secretion in islets of fed and starved rats and its dependence on lipid metabolism. Metab Clin Exp 35:266–271PubMed

30.

Peter-Riesch B, Fathi M, Schlegel W, Wollheim CB (1988) Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets. J Clin Invest 81:1154–1161PubMed

31.

Yaney GC, Korchak HM, Corkey BE (2000) Long-chain acyl CoA regulation of protein kinase C and fatty acid potentiation of glucose-stimulated insulin secretion in clonal β-cells. Endocrinology 141:1989–1998PubMed

32.

Prentki M, Corkey BE (1996) Are the β-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes 45:273–283PubMed

33.

MacDonald MJ (1995) Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets. Further implication of cytosolic NADPH in insulin secretion. J Biol Chem 270:20051–20058PubMed

34.

MacDonald MJ (1993) Estimates of glycolysis, pyruvate (de)carboxylation, pentose phosphate pathway, and methyl succinate metabolism in incapacitated pancreatic islets. Arch Biochem Biophys 305:205–214CrossRefPubMed

35.

MacDonald MJ, McKenzie DI, Walker TM, Kaysen JH (1992) Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. Horm Metab Res 24:158–160PubMed

36.

Brun T, Roche E, Assimacopoulos-Jeannet F, Corkey BE, Kim KH, Prentki M (1996) Evidence for an anaplerotic/malonyl-CoA pathway in pancreatic β-cell nutrient signaling. Diabetes 45:190–198PubMed

37.

Farfari S, Schulz V, Corkey B, Prentki M (2000) Glucose-regulated anaplerosis and cataplerosis in pancreatic β-cells: possible implication of a pyruvate/citrate shuttle in insulin secretion. Diabetes 49:718–726PubMed

38.

Schuit F, De Vos A, Farfari S et al. (1997) Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem 272:18572–18579PubMed

39.

MacDonald MJ, Fahien LA (1990) Insulin release in pancreatic islets by a glycolytic and a Krebs cycle intermediate: contrasting patterns of glyceraldehyde phosphate and succinate. Arch Biochem Biophys 279:104–108PubMed

40.

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

41.

Biden TJ, Taylor KW (1983) Effects of ketone bodies on insulin release and islet-cell metabolism in the rat. Biochem J 212:371–377PubMed

42.

Malaisse WJ, Malaisse-Lagae F, Rasschaert J et al. (1990) The fuel concept for insulin release: regulation of glucose phosphorylation in pancreatic islets. Biochem Soc Trans 18:107–108PubMed

43.

Alcazar O, Qiu-yue Z, Gine E, Tamarit-Rodriguez J (1997) Stimulation of islet protein kinase C translocation by palmitate requires metabolism of the fatty acid. Diabetes 46:1153–1158PubMed

44.

Prentki M, Tornheim K, Corkey BE (1997) Signal transduction mechanisms in nutrient-induced insulin secretion. Diabetalogia 40:S32–S41CrossRef

45.

Aguilar-Bryan L, Nichols CG, Wechsler SW et al. (1995) Cloning of the β-cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 268:423–426PubMed

46.

Seino S, Chen L, Seino M et al. (1992) Cloning of the α1-subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells. Proc Natl Acad Sci USA 89:584–588PubMed

47.

Yaney GC, Wheeler MB, Wei X et al. (1992) Cloning of a novel α1-subunit of the voltage-dependent calcium channel from the β-cell. Mol Endocrinol 6:2143–2152PubMed

48.

Aizawa T, Sato Y, Ishihara F et al. (1994) ATP-sensitive K⁺ channel-independent glucose action in rat pancreatic β-cell. Am J Physiol 266:C622–C627PubMed

49.

Gembal M, Detimary P, Gilon P, Gao ZY, Henquin JC (1993) Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K⁺ channels in mouse B cells. J Clin Invest 91:871–880PubMed

50.

Komatsu M, Schermerhorn T, Aizawa T, Sharp GW (1995) Glucose stimulation of insulin release in the absence of extracellular Ca²⁺ and in the absence of any increase in intracellular Ca²⁺ in rat pancreatic islets. Proc Natl Acad Sci USA 92:10728–10732PubMed

51.

Jonas J-C, Gilon, P and J-C Henquin (1998) Temporal and quantitative corelations between insulin secretion and stably elevated or oscillatory cytoplasmic Ca²⁺ in mouse pancreatic β-cells. Diabetes 47:1266–1273PubMed

52.

Komatsu M, Sharp GW (1998) Palmitate and myristate selectively mimic the effect of glucose in augmenting insulin release in the absence of extracellular Ca²⁺. Diabetes 47:352–357PubMed

53.

Roche E, Farfari S, Witters LA et al. (1998) Long-term Exposure of β-INS cells to high glucose concentrations increases anaplerosis, and lipogenic gene expression. Diabetes 47:1086–1094PubMed

54.

Zhang S, Kim KH (1998) Essential role of acetyl-CoA carboxylase in the glucose-induced insulin secretion in a pancreatic β-cell line. Cell Signal 10:35–42CrossRefPubMed

55.

Tornheim K (1997) Are metabolic oscillations responsible for normal oscillatory insulin secretion? Diabetes 46:1375–1380PubMed

56.

Gumbiner B, Van Cauter E, Beltz WF et al. (1996) Abnormalities of insulin pulsatility and glucose oscillations during meals in obese noninsulin-dependent diabetic patients: effects of weight reduction. J Clin Endocrinol Metab 81:2061–2068PubMed

57.

Porksen N, Hollingdal M, Juhl C, Butler P, Veldhuis JD, Schmitz O (2002) Pulsatile insulin secretion: detection, regulation, and role in diabetes. Diabetes 51:S245–S254PubMed

58.

Nilsson T, Schultz V, Berggren PO, Corkey BE, Tornheim K (1996) Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca²⁺ in glucose-stimulated pancreatic beta-cells. Biochem J 314:91–94PubMed

59.

Deeney JT, Kohler M, Kubik K et al. (2001) Glucose-induced metabolic oscillations parallel those of Ca²⁺ and insulin release in clonal insulin-secreting cells. A multiwell approach to oscillatory cell behavior. J Biol Chem 276:36946–36950CrossRefPubMed

60.

Civelek VN, Deeney JT, Shalosky NJ et al. (1996) Regulation of β-cell mitochondrial function: Influence of Ca²⁺, substrate, and ADP on oxygen consumption by permeabilized clonal pancreatic β-cells. Biochem J 318:615–621PubMed

61.

Yaney GC, Schultz V, Cunningham BA, Dunaway GA, Corkey BE, Tornheim K (1995) Phosphofructokinase isozymes in pancreatic islets and clonal β-cells (INS-1). Diabetes 44:1285–1289PubMed

62.

Civelek VN, Deeney JT, Kubik K, Schultz V, Tornheim K, Corkey BE (1996) Temporal sequence of metabolic and ionic events in glucose-stimulated clonal pancreatic beta-cells (HIT). Biochem J 315:1015–1019PubMed

63.

Larsson O, Deeney JT, Bränström R, Berggren PO, Corkey BE (1996) Activation of the ATP-sensitive K⁺ channel by long chain acyl-CoA. A role in modulation of pancreatic β-cell glucose sensitivity. J Biol Chem 271:10623–10626CrossRefPubMed

64.

Branstrom R, Leibiger IB, Leibiger B, Corkey BE, Berggren PO, Larsson O (1998) Long chain coenzyme A esters activate the pore-forming subunit (Kir6. 2) of the ATP-regulated potassium channel. J Biol Chem 273:31395–31400CrossRefPubMed

65.

Bränström R, Corkey BE, Berggren PO, Larsson O (1997) Evidence for a unique long chain acyl-CoA ester binding site on the ATP-regulated potassium channel in mouse pancreatic β-cells. J Biol Chem 272:17390–17394CrossRefPubMed

66.

Gribble FM, Proks P, Corkey BE, Ashcroft FM (1998) Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. J Biol Chem 273:26383–26387CrossRefPubMed

67.

Malaisse WJ, Best L, Kawazu S, Malaisse-Lagae F, Sener A (1983) The stimulus-secretion coupling of glucose-induced insulin release: fuel metabolism in islets deprived of exogenous nutrient. Arch Biochem Biophys 224:102–110PubMed

68.

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

69.

Deeney JT, Gromada J, Hoy M et al. (2000) Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI beta-cells). J Biol Chem 275:9363–9368CrossRefPubMed

70.

Hamilton JA, Kamp F (1999) How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes 48:2255–2269PubMed

71.

Grupping AY, Cnop M, Van Schravendijk CF, Hannaert JC, Van Berkel TJ, Pipeleers DG (1997) Low density lipoprotein binding and uptake by human and rat islet beta cells. Endocrinology 138:4064–4068PubMed

72.

Cruz WS, Kwon G, Marshall CA, McDaniel ML, Semenkovich CF (2001) Glucose and insulin stimulate heparin-releasable lipoprotein lipase activity in mouse islets and INS-1 cells. A potential link between insulin resistance and β-cell dysfunction. J Biol Chem 276:12162–12168CrossRefPubMed

73.

McGarry JD, Sen A, Esser V, Woeltje KF, Weis B, Foster DW (1991) New insights into the mitochondrial carnitine palmitoyltransferase enzyme system. Biochimie 73:77–84CrossRefPubMed

74.

Boylan JG, Hamilton JA (1992) Interactions of acyl-coenzyme A with phosphatidylcholine bilayers and serum albumin. Biochemistry 31:557–567PubMed

75.

Corkey BE, Deeney JT (1990) Acyl CoA regulation of metabolism and signal transduction. Prog Clin Biol Res 321:217–232PubMed

76.

Corkey B (1988) Analysis of acyl-coenzyme A esters in biological samples. Methods Enzymol 166:55–70PubMed

77.

Deeney JT, Tornheim K, Korchak HM, Prentki M, Corkey BE (1992) Acyl-CoA esters modulate intracellular Ca²⁺ handling by permeabilized clonal pancreatic β-cells. J Biol Chem 267:19840–19845PubMed

78.

Warnotte C, Gilon P, Nenquin M, Henquin J-C (1994) Mechanisms of the stimulation of insulin release by saturated fatty acids. Astudy of palmiate in mouse β-cells. Diabetes 43:703–711

79.

Warnotte C, Nenquin M, Henquin JC (1999) Unbound rather than total concentration and saturation rather than unsaturation determine the potency of fatty acids on insulin secretion. Mol Cell Endocrinol 153:147–153PubMed

80.

Gravena C, Mathias PC, Ashcroft SJ (2002) Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans. J Endocrinol 173:73–80PubMed

81.

Crespin SR, Greenough WB 3rd, Steinberg D (1969) Stimulation of insulin secretion by infusion of free fatty acids. J Clin Invest 48:1934–1943PubMed

82.

Paolisso G, Gambardella A, Amato L et al. (1995) Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects. Diabetologia 38:1295–1299PubMed

83.

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

84.

Vara E, Fernandez-Martin O, Garcia C, Tamarit-Rodriguez J (1988) Palmitate dependence of insulin secretion, "de novo" phospholipid synthesis and⁴⁵Ca²⁺-turnover in glucose stimulated rat islets. Diabetologia 31:687–693PubMed

85.

Thams P, Capito K (2001) Differential mechanisms of glucose and palmitate in augmentation of insulin secretion in mouse pancreatic islets. Diabetologia 44:738–746CrossRefPubMed

86.

Dobbins RL, Chester MW, Stevenson BE, Daniels MB, Stein DT, McGarry JD (1998) A fatty acid-dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion. J Clin Invest 101:2370–2376PubMed

87.

Ramanadham S, Hsu F, Zhang S, Bohrer A, Ma Z, Turk J (2000) Electrospray ionization mass spectrometric analyses of phospholipids from INS-1 insulinoma cells: comparison to pancreatic islets and effects of fatty acid supplementation on phospholipid composition and insulin secretion. Biochim Biophys Acta 1484:251–266CrossRefPubMed

88.

Ramanadham S, Hsu FF, Bohrer A, Ma Z, Turk J (1999) Studies of the role of group VI phospholipase A2 in fatty acid incorporation, phospholipid remodeling, lysophosphatidylcholine generation, and secretagogue-induced arachidonic acid release in pancreatic islets and insulinoma cells. J Biol Chem 274:13915–13927CrossRefPubMed

89.

Opara EC, Garfinkel M, Hubbard VS, Burch WM, Akwari OE (1994) Effect of fatty acids on insulin release: role of chain length and degree of unsaturation. Am J Physiol 266:E635–E639PubMed

90.

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

91.

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

92.

Stein DT, Esser V, Stevenson BE et al. (1996) Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 97:2728–2735PubMed

93.

Roduit R, Masiello P, Wang SP, Li H, Mitchell GA, Prentki M (2001) A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. Diabetes 50:1970–1975PubMed

94.

Yajima H, Komatsu M, Yamada S et al. (2000) Cerulenin, an inhibitor of protein acylation, selectively attenuates nutrient stimulation of insulin release: a study in rat pancreatic islets. Diabetes 49:712–717PubMed

95.

Sako Y, Grill VE (1990) A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology 127:1580–1589PubMed

96.

Carpentier A, Mittelman SD, Lamarche B, Bergman RN, Giacca A, Lewis GF (1999) Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation. Am J Physiol 276:E1055–E1066PubMed

97.

Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y, Uchino H, Giacca A, McGarry JD (2002) The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51:1825–1833PubMed

98.

Marshall JA, Bessesen DH, Hamman RF (1997) High saturated fat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: the San Luis Valley Diabetes Study. Diabetologia 40:430–438CrossRefPubMed

99.

Majumdar S, Rossi MW, Fujiki T et al. (1991) Protein kinase C isotypes and signaling in neutrophils. Differential substrate specificities of a translocatable calcium- and phospholipid-dependent beta-protein kinase C and a phospholipid-dependent protein kinase which is inhibited by long chain fatty acyl coenzyme A. J Biol Chem 266:9285–9294PubMed

100.

Woldegiorgis G, Yousufzai SY, Shrago E (1982) Studies on the interaction of palmitoyl coenzyme A with the adenine nucleotide translocase. J Biol Chem 257:14783–14787PubMed

101.

Tippett PS, Neet KE (1982) Specific inhibition of glucokinase by long chain acyl coenzymes A below the critical micelle concentration. J Biol Chem 257:12839–12845PubMed

102.

Brun T, Assimacopoulos-Jeannet F, Corkey BE, Prentki M (1997) Long-chain fatty acids inhibit acetyl-CoA carboxylase gene expression in the pancreatic β-cell line INS-1. Diabetes 46:393–400PubMed

103.

Assimacopoulos-Jeannet F, Thumelin S, Roche E, Esser V, McGarry JD, Prentki M (1997) Fatty acids rapidly induce the carnitine palmitoyltransferase I gene in the pancreatic beta-cell line INS-1. J Biol Chem 272:1659–1664CrossRefPubMed

104.

Liu YQ, Tornheim K, Leahy JL (1998) Fatty acid-induced beta cell hypersensitivity to glucose. Increased phosphofructokinase activity and lowered glucose-6-phosphate content. J Clin Invest 101:1870–1875PubMed

105.

Liu YQ, Tornheim K, Leahy JL (1998) Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity. Diabetes 47:1889–1893PubMed

106.

Bollheimer LC, Skelly RH, Chester MW, McGarry JD, Rhodes CJ (1998) Chronic exposure to free fatty acid reduces pancreatic beta cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation. J Clin Invest 101:1094–1101PubMed

107.

Gremlich S, Bonny C, Waeber G, Thorens B (1997) Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. J Biol Chem 272:30261–30269CrossRefPubMed

108.

Bjorklund A, Yaney G, McGarry JD, Weir G (1997) Fatty acids and β-cell function. Diabetologia 40:B21–B26CrossRefPubMed

109.

Mulder H, Holst LS, Svensson H et al. (1999) Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in β-cells. Diabetes 48:228–232PubMed

110.

Winzell MS, Svensson H, Arner P, Ahren B, Holm C (2001) The expression of hormone-sensitive lipase in clonal β-cells and rat islets is induced by long-term exposure to high glucose. Diabetes 50:2225–2230PubMed

111.

Holm C, Osterlund T, Laurell H, Contreras JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr 20:365–393CrossRefPubMed

112.

Masiello P, Novelli M, Bombara M et al. (2002) The antilipolytic agent 3,5-dimethylpyrazole inhibits insulin release in response to both nutrient secretagogues and cyclic adenosine monophosphate agonists in isolated rat islets. Metab Clin Exp 51:110–114CrossRefPubMed

113.

Yaney GC, Civelek VN, Richard AM et al. (2001) Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic β-cells (HIT). Diabetes 50:56–62PubMed

114.

Cunningham BA, Richard AM, Dillon JS et al. (2003) Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets. Biochem J 369:173–178CrossRefPubMed

115.

Haemmerle G, Zimmermann R, Hayn M et al. (2002) Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 277:4806–4815CrossRefPubMed

116.

Faergeman NJ, Knudsen J (1997) Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J 323:1–12PubMed

117.

Metz SA, Dunlop M (1990) Stimulation of insulin release by phospholipase D. A potential role for endogenous phosphatidic acid in pancreatic islet function. Biochem J 270:427–435PubMed

118.

Hodgkin MN, Pettitt TR, Martin A, Michell RH, Pemberton AJ, Wakelam MJ (1998) Diacylglycerols and phosphatidates: which molecular species are intracellular messengers? Trends Biochem Sci (TIBS) 23:200–204CrossRef

119.

Goetzl EJ (2001) Pleiotypic mechanisms of cellular responses to biologically active lysophospholipids. Prostaglandins Other Lipid Mediat 64:11–20CrossRefPubMed

120.

Eddlestone GT (1995) ATP-sensitive K channel modulation by products of PLA2 action in the insulin-secreting HIT cell line. Am J Physiol 268:C181–C90PubMed

121.

Baukrowitz T, Fakler B (2000) K(ATP) channels: linker between phospholipid metabolism and excitability. Biochem Pharmacol 60:735–740CrossRefPubMed

122.

Severson DL, Hurley B (1984) Inhibition of the hormone-sensitive lipase in adipose tissue by long-chain fatty acyl coenzyme A. Lipids 19:134–138PubMed

123.

Kindmark H, Kohler M, Efendic S, Rorsman P, Larsson O, Berggren PO (1992) Protein kinase C activity affects glucose-induced oscillations in cytoplasmic free Ca²⁺ in the pancreatic β-cell. FEBS Lett 303:85–90CrossRefPubMed

124.

Lawrie AM, Toescu EC, Gallacher DV (1993) Two different spatiotemporal patterns for Ca²⁺ oscillations in pancreatic acinar cells: evidence of a role for protein kinase C in Ins(1,4,5)P3-mediated Ca²⁺ signalling. Cell Calcium 14:698–710PubMed

125.

Martin F, Reig JA, Soria B (1995) Secretagogue-induced [Ca²⁺]i changes in single rat pancreatic islets and correlation with simultaneously measured insulin release. J Mol Endocrinol 15:177–185PubMed

126.

Nakazaki M, Ishihara H, Kakei M et al. (1998) Repetitive mitochondrial Ca²⁺ signals synchronize with cytosolic Ca²⁺ oscillations in the pancreatic β-cell line, MIN6. Diabetologia 41:279–286CrossRefPubMed

127.

Takahashi M, Seagar MJ, Jones JF, Reber BF, Catterall WA (1987) Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci USA 84:5478–5482PubMed

128.

Satin LS, Tavalin SJ, Kinard TA, Teague J (1995) Contribution of L- and non-L-type calcium channels to voltage-gated calcium current and glucose-dependent insulin secretion in HIT-T15 cells. Endocrinology 136:4589–4601PubMed

129.

Ihara Y, Yamada Y, Fujii Y et al. (1995) Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells. Mol Endocrinol 9:121–130PubMed

130.

Sollner TH, Rothman JE (1996) Molecular machinery mediating vesicle budding, docking and fusion. Experientia 52:1021–1025PubMed

131.

Rorsman P, Eliasson L, Renstrom E, Gromada J, Barg S, Gopel S (2000) The cell physiology of biphasic insulin secretion. News Physiol Sci 15:72–77PubMed

132.

Daniel S, Noda M, Straub SG, Sharp GWG (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulted insulin secretion. Diabetes 48:1686–1690PubMed

133.

Tsubamoto Y, Eto K, Noda M et al. (2001) Hexamminecobalt(III) chloride inhibits glucose-induced insulin secretion at the exocytotic process. J Biol Chem 276:2979–2985CrossRefPubMed

134.

Newton AC, Johnson JE (1998) Protein kinase C: a paradigm for regulation of protein function by two membrane-targeting modules. Biochim Biophys Acta 1376:155–172CrossRefPubMed

135.

Ford DA, Horner CC, Gross RW (1998) Protein kinase C acylation by palmitoyl coenzyme A facilitates its translocation to membranes. Biochemistry 37:11953–11961CrossRefPubMed

136.

Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161–167CrossRefPubMed

137.

Knutson KL, Hoenig M (1994) Identification and subcellular characterization of protein kinase-C isoforms in insulinoma beta-cells and whole islets. Endocrinology 135:881–886PubMed

138.

Tian YM, Urquidi V, Ashcroft SJ (1996) Protein kinase C in β-cells: expression of multiple isoforms and involvement in cholinergic stimulation of insulin secretion. Mol Cell Endocrinol 119:185–193CrossRefPubMed

139.

Zawalich WS, Zawalich KC (1996) Regulation of insulin secretion by phospholipase C. Am J Physiol 271:E409–E416PubMed

140.

Zawalich WS, Bonnet-Eymard M, Zawalich KC, Yaney GC (1998) Chronic exposure to TPA depletes PKC-α and augments Ca-dependent insulin secretion from cultured rat islets. Am J Physiol 274:C1388–C1396PubMed

141.

Deeney JT, Cunningham BA, Chheda S et al. (1996) Reversible Ca²⁺-dependent translocation of protein kinase C and glucose-induced insulin release. J Biol Chem 271:18154–18160CrossRefPubMed

142.

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 85:482–490PubMed

143.

Ganesan S, Calle R, Zawalich K, Smallwood JI, Zawalich WS, Rasmussen H (1990) Glucose-induced translocation of protein kinase C in rat pancreatic islets. Proc Natl Acad Sci USA 87:9893–9897PubMed

144.

Ganesan S, Calle R, Zawalich K et al. (1992) Immunocytochemical localization of alpha-protein kinase C in rat pancreatic β-cells during glucose-induced insulin secretion. J Cell Biol 119:313–324PubMed

145.

Yedovitzky M, Mochly-Rosen D, Johnson JA et al. (1997) Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic β-cells. J Biol Chem 272:1417–1420CrossRefPubMed

146.

Yaney GC, Fairbanks JM, Deeney JT, Korchak HM, Tornheim K, Corkey BE (2002) Potentiation of insulin secretion by phorbol esters is mediated by PKC-α and nPKC isoforms. Am J Physiol 283:E880–E888

147.

Littman ED, Pitchumoni S, Garfinkel MR, Opara EC (2000) Role of protein kinase C isoenzymes in fatty acid stimulation of insulin secretion. Pancreas 20:256–263CrossRefPubMed

148.

Limatola C, Schaap D, Moolenaar WH, van Blitterswijk WJ (1994) Phosphatidic acid activation of protein kinase C-ζ overexpressed in COS cells: comparison with other protein kinase C isotypes and other acidic lipids. Biochem J 304:1001–1008PubMed

149.

Nakanishi H, Brewer KA, Exton JH (1993) Activation of the ζ isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 268:13–16PubMed

150.

Chou MM, Hou W, Johnson J et al. (1998) Regulation of protein kinase C ζ by PI 3-kinase and PDK-1. Curr Biol 8:1069–1077

151.

Khan WA, Blobe G, Halpern A et al. (1993) Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets. J Biol Chem 268:5063–5068PubMed

152.

Shirai Y, Kashiwagi K, Yagi K, Sakai N, Saito N (1998) Distinct effects of fatty acids on translocation of γ- and ε-subspecies of protein kinase C. J Cell Biol 143:511–521PubMed

153.

Gillis KD, Mossner R, Neher E (1996) Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules. Neuron 16:1209–1220PubMed

154.

Stevens CF, Sullivan JM (1998) Regulation of the readily releasable vesicle pool by protein kinase C. Neuron 21:885–893PubMed

155.

Chen YA, Duvvuri V, Schulman H, Scheller RH (1999) Calmodulin and protein kinase C increase Ca²⁺-stimulated secretion by modulating membrane-attached exocytic machinery. J Biol Chem 274:26469–26476CrossRefPubMed

156.

Yu W, Niwa T, Fukasawa T et al. (2000) Synergism of protein kinase A, protein kinase C, and myosin light-chain kinase in the secretory cascade of the pancreatic β-cell. Diabetes 49:945–952PubMed

157.

Hisatomi M, Hidaka H, Niki I (1996) Ca²⁺/calmodulin and cyclic 3,5′ adenosine monophosphate control movement of secretory granules through protein phosphorylation/dephosphorylation in the pancreatic β-cell. Endocrinology 137:4644–4649PubMed

158.

Tian Y, Laychock SG (2001) Protein kinase C and calcium regulation of adenylyl cyclase in isolated rat pancreatic islets. Diabetes 50:2505–2513PubMed

159.

Sharp GW (1979) The adenylate cyclase-cyclic AMP system in islets of Langerhans and its role in the control of insulin release. Diabetologia 16:287–296PubMed

160.

Regazzi R, Li G, Ullrich S, Jaggi C, Wollheim CB (1989) Different requirements for protein kinase C activation and Ca²⁺-independent insulin secretion in response to guanine nucleotides. Endogenously generated diacylglycerol requires elevated Ca²⁺ for kinase C insertion into membranes. J Biol Chem 264:9939–9944PubMed

161.

Fujita Y, Sasaki T, Fukui K et al. (1996) Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin. J Biol Chem 271:7265–7268CrossRefPubMed

162.

Shimazaki Y, Nishiki T, Omori A et al. (1996) Phosphorylation of 25-kDa synaptosome-associated protein. Possible involvement in protein kinase C-mediated regulation of neurotransmitter release. J Biol Chem 271:14548–14553CrossRefPubMed

163.

Hartwig JH, Thelen M, Rosen A, Jammey PA, Nairn AC, Aderem A (1992) MARCKS is an actin filament crosslinking protein regulated by PKC and calcium-calmodulin. Nature 356:618–622CrossRefPubMed

164.

Vitale ML, Seward EP, Trifaro JM (1995) Chromaffin cell cortical actin network dynamics control the size of the release-ready vesicle pool and the initial rate of exocytosis. Neuron 14:353–363PubMed

165.

Nishizaki T, Walent JH, Kowalchyk JA, Martin TF (1992) A key role for a 145-kDa cytosolic protein in the stimulation of Ca²⁺-dependent secretion by protein kinase C. J Biol Chem 267:23972–23981PubMed

166.

Wiser O, Trus M, Hernandez A et al. (1999) The voltage sensitive Lc-type Ca²⁺ channel is functionally coupled to the exocytotic machinery. Proc Natl Acad Sci USA 96:248–253CrossRefPubMed

167.

Yang SN, Larsson O, Branstrom R et al. (1999) Syntaxin 1 interacts with the L(D) subtype of voltage-gated Ca²⁺ channels in pancreatic β-cells. Proc Natl Acad Sci USA 96:10164–10169CrossRefPubMed

168.

Arkhammar P, Juntti BL, Larsson O et al. (1994) Protein kinase C modulates the insulin secretory process by maintaining a proper function of the beta-cell voltage-activated Ca²⁺ channels. J Biol Chem 269:2743–2749PubMed

169.

Yang J, Tsien RW (1993) Enhancement of N- and L-type calcium channel currents by protein kinase C in frog sympathetic neurons. Neuron 10:127–136PubMed

170.

McHugh D, Sharp EM, Scheuer T, Catterall WA (2000) Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain. Proc Natl Acad Sci USA 97:12334–12338CrossRefPubMed

171.

Pfanner N, Orci L, Glick BS et al. (1989) Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae. Cell 59:95–102PubMed

172.

Pfanner N, Glick BS, Arden SR, Rothman JE (1990) Fatty acylation promotes fusion of transport vesicles with Golgi cisternae. J Cell Biol 110:955–961PubMed

173.

Gonelle-Gispert C, Molinete M, Halban PA, Sadoul K (2000) Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells. J Cell Sci 113:3197–3205PubMed

174.

Vogel K, Cabaniols JP, Roche PA (2000) Targeting of SNAP-25 to membranes is mediated by its association with the target SNARE syntaxin. J Biol Chem 275:2959–2965PubMed

175.

Washbourne P, Cansino V, Mathews JR, Graham M, Burgoyne RD, Wilson MC (2001) Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting. Biochem J 357:625–634CrossRefPubMed

176.

Gonzalo S, Linder ME (1998) SNAP-25 palmitoylation and plasma membrane targeting require a functional secretory pathway. Mol Biol Cell 9:585–597PubMed

177.

Veit M, Becher A, Ahnert-Hilger G (2000) Synaptobrevin 2 is palmitoylated in synaptic vesicles prepared from adult, but not from embryonic brain. Mol Cell Neurosci 15:408–416CrossRefPubMed

178.

Veit M, Sollner TH, Rothman JE (1996) Multiple palmitoylation of synaptotagmin and the t-SNARE SNAP-25. FEBS Lett 385:119–123CrossRefPubMed

179.

Chien AJ, Gao T, Perez-Reyes E, Hosey MM (1998) Membrane targeting of L-type calcium channels. Role of palmitoylation in the subcellular localization of the β2a subunit. J Biol Chem 273:23590–23597CrossRefPubMed

180.

Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106:473–481PubMed

181.

Alemzadeh R, Langley G, Upchurch L, Smith P, Slonim AE (1998) Beneficial effect of diazoxide in obese hyperinsulinemic adults. J Clin Endocrinol Metab 83:1911–1915

Titel: Fatty acid metabolism and insulin secretion in pancreatic beta cells
verfasst von: G. C. Yaney
Dr. B. E. Corkey
Publikationsdatum: 01.10.2003
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2003
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-003-1207-4

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Fatty acid metabolism and insulin secretion in pancreatic beta cells

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