Interactions between glucose and FFA metabolism in man

Diabetes/Metabolism Reviews

Volumn 12, Issue 1, 1996, Pages 15-36

  Saloranta, Carola ^a,c   Groop, Leif ^b  

^a HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^b LUND UNIVERSITY   (Sweden)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN;

DIABETES MELLITUS; ETIOLOGY; FATTY ACID METABOLISM; GLUCOSE METABOLISM; HUMAN; PRIORITY JOURNAL; REVIEW;

EID: 0029886961     PISSN: 07424221     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-0895(199603)12:1<15::AID-DMR153>3.3.CO;2-S     Document Type: Review

References (187)

1. Groop LC, Widén E, and Ferrannini E: Insulin resistance and insulin efficiency in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: errors of metabolism or of methods? Diabetologia 36:1326-1331, 1993.
2. DeFronzo RA, Tobin JD, and Andres R: Glucose clamp technique: a method for quantifying insu- lin secretion and resistance. Am J Physiol 237: E214-E223, 1979.
3. Matthews DR and Hosker JP: Unbiased and flexible computer program to achieve glucose clamping. Diabetes Care 12: 156-159, 1989.
4. Verdonk CA, Rizza RA, Westland RE, Nelson RL, Gerieh JE, and Service FJ: Glucose clamping using the Biostator GCIIS. Harm Metab Res 12: 133-135, 1980:
5. Shulman GI, Ladenson PW, Wolfe MH, Ridgway EC, and Wolfe RR: Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man. J Clin Invest 76: 757-764, 1985.
6. Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, and Shulman RG: Quantitation of muscle glycogen synthesis in normal subjects and subjects, with non-insulin-dependent diabetes by (+13)C nuclear magnetic resonance spectroscopy. N Engl J Med 322: 223-228, 1990.
7. Wolfe BM, Klein S, Peters EJ, Schmidt BF, and Wolfe RR: Effect of elevated fatty acids on glucose oxidation in normal humans. Metabolism 37: 323-329, 1988.
8. Rossetti L and Giaccari A: Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake: a dose-response euglycemic clamp study in normal and diabetic rats. J Clin Invest 85: 1785-1792, 1990.
9. Kelly DE, Mokan M, Simoneau J-A, and Mandarino LJ: Interaction between glucose and free fatty acid metabolism in human skeletal muscle. J Clin Invest 92: 91-98, 1983.
10. Ferrannini E, Del Prato S, De Fronzo RA: Glucose kinetics; Tracer methods. In Methods in Diabetes Research, Volume II: Clinical methods. Clarke WL, Larner J and Pohl SL (Eds). John Wiley & Sons, New York, 1986, pp 108-141.
11. Ferrannini E, Smith D, Cobelli C, Toffolo G, Pilo A, and DeFronzo RA: Effect of insulin on the distribution and disposition of glucose in man. J Clin Invest 76: 357-364, 1985.
12. Hother-Nielson O, Mengel A, Möller J, Rasmussen O, Schmitz O, and Beck-Nielsen H: Assessment of glucose turnover rates in euglycaemic clamp studies using primed-constant (3-(+3)H)glucose infusion and labelled or unlabelled glucose infusates. Diabetic Med 9: 840-849, 1992.
13. Finegood DT, Bergman R, and Vranic M: Modelling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps. Diabetes 37: 1025-1034, 1988.
14. Norwich KH: Measuring rates of appearance in systems which are not in steady state. Can J Physiol Pharmacol 51: 91-101, 1973.
15. Boden G, Chen X, Ruiz J, White JV, and Rossetti L: Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93: 2438-2446, 1994.
16. Hagenfeldt L: Turnover of individual free fatty acids in man. Fed Proc 34: 2246-2249, 1975.
17. Hagenfeldt L, Wahren J, Pernow B, and Räf L: Uptake of individual free fatty acids by skeletal musde and liver in man. J Clin Invest 51: 2324-2330, 1972.
18. Miles JM, Ellman MG, McLean KL, and Jensen MD: Validation of a new method for determination of turnover of free fatty acid. Am J Physiol 252: E431-E438, 1987.
19. Shapiro B, Chowers I, and Rose G: Fatty acid uptake and esterification in adipose tissue. Biochem Biophys Acta 23: 115-120, 1957.
20. Campbell PJ, Carlson MG, Hill JO, Nurjhan N: Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and re-esterification. Am J Physiol 263: 1063-1069, 1992.
21. Carlson M, Snead WL, Hill JO, Nurjhan N, and Campbell PJ: Glucose regulation of lipid metabolism in humans. Am J Physiol 261: E815-E820, 1991.
22. Carlson M, Snead WL, and Campbell PJ: Regulation of free fatty acid metabolism by glucagon. J Clin Endocrinol Metab 77: 11-15, 1993.
23. Groop LC, Bonadonna RC, DelPrato S, Ratheiser K, Zych K, Ferrannini E, and DeFronzo RA: Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus: evidence for multiple sites of insulin resistance. J Clin Invest 84: 205-213, 1989.
24. Issekutz B Jr, Bortz WM, Miller HI, and Paul P: Turnover rate of FFA in humans and in dogs. Metab Clin Exp 16: 1001-1009, 1967.
25. Dagenais GR, Tancredi RG, and Zierler KL: Free fatty acid oxidation by forearm muscle at rest and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest 58: 421-431, 1976.
26. Groop LC, Bonadonna RC, Petrides AS, and DeFronzo RA: Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man. J Clin Invest 87: 83-89, 1991.
27. Yki-Järvinen H, Puhakainen I, Saloranta C, and Taskinen M-R: Demonstration of a novel feedback mechanism between FFA oxidation from intracellular and intravascular sources. Am J Physiol 260: 680-689, 1991.
28. Helling VJ, Miles JM, and Jensen MD: How valid are isotopic measurements of fatty acid oxidation? Am J Physiol 261: E572-E577, 1991.
29. Basso LV and Havel RJ: Hepatic metabolism of free fatty acids in normal and diabetic dogs. J Clin Invest 49: 537-547, 1970.
30. Hurley BF, Nemeth PM, Martin III WH, Hagberg JM, Dalsky GP, and Hoiloszy JO: Muscle triglyceride utilization during exercise: effect of training. J Appl Physiol 60: 562-567, 1986.
31. Falholt K, Jensen I, Lindkaer Jensen S, Mortensen H, Völund A, Heding LG, Noerskov Petersen P, and Falholt W: Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients. Diabetic Med 5: 27-31, 1987.
32. Crass MF, McCaskill ES, Shipp JC, and Murthy VK: Metabolism of endogenous lipids in cardiac muscle: effect of pressure development. Am J Physiol 220: 428-435, 1971.
33. Randle PJ, Garland PB, Hales CN, and News- holme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet i: 785-789, 1963.
34. Neely JR and Morgan HE: Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 36: 413-459, 1974.
35. Rennie MJ and Holloszy JO: Inhibition of glucose uptake and glycogenolysis by availability of oleate in well-oxygenated perfused skeletal muscle. Biochem J 168: 161-170, 1977.
36. Cuendet GS, Loten EG, and Renold AE: Evidence that the glucose fatty acid is operative in isolated skeletal (soleus) muscle. Diabetologia 12: 336, 1975.
37. Maizels EZ, Ruderman MB, Goodman MN, and Lau D: Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat. Biochem J 162: 557-568, 1977.
38. Schonfield G and Kipnis DM: Effects of fatty acids on carbohydrate and fatty acid metabolism of rat diaphragm. Am. J Physiol 215: 513-522, 1968.
39. Beatty CH and Bocek RM: Interrelation of carbohydrate and palmitate metabolism in skeletal muscle. Am J Physiol 220: 1928-1934, 1971.
40. Goodman MN, Berger M, and Ruderman NB: Glucose metabolism in rat skeletal muscle at rest: effect of starvation, diabetes, ketone bodies and free fatty acids. Diabetes 23: 881-888, 1974.
41. Reimer F, Löffier G, Henning G, and Wieland OH: The influence of insulin on glucose and fatty acid metabolism in the isolated perfused rat hind quarter. Hoppe-Seyler's Z Phsyiol Chem 356: 1055-1066, 1975.
42. Jefferson LSJ, Kochler JO, and Morgan HE: Effect of insulin on protein synthesis in skeletal muscle of isolated perfused preparation of rat hemicorpus. Proc Natl Acad Sci USA 69: 816-820, 1972.
43. Ruderman N, Kemmer FW, Goodman MN, and Berger M: Oxygen consumption in perfused skeletal muscle: effect of perfusion with aged, fresh and aged-rejuvenated erythrocytes on oxygen consumption, tissue metabolites and inhibition of glucose utilization by acetoacetate. Biochem J 190: 57-64, 1980.
44. Argyraki M, Wright PD, Venables CV, Proud G, and Taylor R: In vitro study of human skeletal muscle strips: effect of nonesterified fatty acid supply on glucose storage. Metabolism 38: 1183-1187, 1989.
45. Paul B, Issekutz B Jr, and Miller HI: Interrelationships of free fatty acids and glucose metabolism in the dog. Am J Physiol 211: 1313-1320, 1966.
46. Seyffert WA Jr, and Madison LL: Physiologic effects of metabolic fuels on carbohydrate metabolism. I. Acute effect of elevation of plasma free fatty acids on hepatic glucose output, peripheral glucose utilization, serum insulin, and plasma glucagon levels. Diabetes 16: 765-776, 1967.
47. Jenkins AB, Storlien LH, Chishplm DJ, and Kraegen EW: Effects of non-esterified fatty acid availability on tissue-specific glucose utilization in rats in vivo. J Clin Invest 82: 293-299, 1988.
48. Kruszynska YT, McCormack JG, and Mclntyre N: Effects of glycogen stores and non-esterified fatty acid availability on insulin-stimulated glucose metabolism and tissue pyruvate dehydrogenase activity in the rat. Diabetologia 34: 205-211, 1991.
49. Felber JP, and Vannotti A: Effects of fat infusion on glucose tolerance and plasma insulin levels. Med Exp 10: 153-156, 1964.
50. Nestel PJ, Carroll KF, and Silverstein MS: Influence of free fatty acid metabolism on glucose tolerance. Lancet ii: 115-117, 1964.
51. Schalch DS and Kipnis DM: Abnormalities in carbohydrate tolerance associated with elevated plasma nonesterified fatty acids. J Clin Invest 44: 2010-2020, 1965.
52. Gómez F, Jéquier E, Chabot V, Byber V, and Felber J-P: Carbohydrate and lipid oxidation in normal human subjects: its influence on glucose tolerance and insulin response to glucose. Metabolism 21: 381-391, 1972.
53. Balasse EO and Neef MA: Operation of the "glucose-fatty acid cycle" during experimental elevations of plasma free fatty acid levels in man. Eur J Clin Invest 4: 247-252, 1974.
54. Rousselle J, Buekert A, Pahud P, Jéquier E, and Felber JP: Relationship between glucose oxidation and glucose tolerance in man. Metabolism 31: 866-870, 1982.
55. Ferrannini E, Barrett EJ, Bevilacqua S, and DeFronzo RA: Effect of fatty acids on glucose production and utilization in man. J Clin Invest 72: 1737-1747, 1983.
56. Thièbaud D, DeFronzo RA, Jacot E, Golay A, Acheson K, Maeder E, Jéquier E, and Felber JP: Effect of long-chain triglyceride infusion on glucose metabolism in man. Metabolism 31: 1128-1136, 1982.
57. Bonadonna RC, Zych K, Boni C, Ferrannini E, and DeFronzo RA: Time dependence of the inter-action between lipid and glucose in humans. Am J Physiol 255: E49-E56, 1989.
58. Baron AD, Brechtel G, and Edelman SV: Effects of free fatty acids and ketone bodies on in vivo non-insulin-mediated glucose utilization and production in humans. Metabolism 38: 1056-1061, 1989.
59. Yki-Järvinen H, Puhakainen I, and Koivisto VA: Effect of free fatty acids on glucose uptake and non-oxidative glycolysis across human forearm tissues in the basal state and during insulin stimulation. J Clin Endocrinol Metal 72: 1268-1277, 1991.
60. Walker M, Fulcher GR, Sum CF, Orskov H, and Alberti KGMM: Effect of glycemia and non-esterified fatty acids on fore-arm glucose uptake in normal humans. Am J Physiol 261: E304-E311, 1991.
61. Boden G, Jadali F, White J, Liang Y, Mozzoli M, Chen X, Coleman E, and Smith C: Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J Clin Invest 88: 960-966, 1991.
62. Boden G and Jadali F: Effects of lipid on basal carbohydrate metabolism in normal men. Diabetes 40: 686-692, 1991.
63. Piatti PM, Monti LD, Pacchioni M, Pontiroli AE, and Pozza G: Forearm insulin- and non-insulin-mediated glucose uptake and muscle metabolism in man: role of free fatty acids and blood glucose levels. Metabolism 40: 926-933, 1991.
64. Nuutila P, Koivisto VA, Knuuti J, Ruotsalainen U, Teräs M, Haaparanta M, Bergman J, Solin O, Voipio-Pulkki L-M, Wegelius U, and Yki-Järvinen H. Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo. J Clin Invest 89: 1767-1774, 1992.
65. Saloranta C, Koivisto V, Widén E. Falholt K, DeFronzo RA, Härkönen M, and Groop L: Contribution of muscle and liver to glucose/fatty acid cycle in humans. Am J Physiol 264: E599-E605-1993.
66. Johnson AB, Argyraki M, Thow JC, Cooper BG, Fulcher G, and Taylor R: Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man. Clin Sci 82: 219-226, 1992.
67. Yki-Järvinen H: Action of insulin on glucose metabolism in vivo. Baillière's Clin Endocrinol Metab 7: 903-926, 1993.
68. Nuutila P, Knuuti U, Ruotsalainen U, Teräs M, Voipio-Pulkki L-M, Haaparanta M, Solin O, Wegelius U, and Yki-Järvinen H: Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans. Am J Physiol 267: E941-E946, 1994.
69. DeFronzo RA, Jacot E, Jéquier E, Maeder E, Wahren J, and Felber JP: The effect of insulin on the disposal of intravenous glucose: results from indirect calorimetry and hepatic and femoral venous atheterization. Diabetes 30: 1000-1007, 1981.
70. Felley CP, Felley EM, and van Meile GD: Impairment of glucose disposal by infusion of triglycerides in humans: role of glycemia. Am J Physiol 256: E747-E752, 1989.
71. Bevilacqua S, Bonadonna RC, Buzzigoli G, Boni C, Ciociaro D, Maccari F, Giorico MA, and Ferrannini E: Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism 36: 502-506, 1987.
72. Bevilacqua S, Buzzigoli G, Bonadonna RC, Brandi M, Oleggini C, Boni C, Geloni M, and Ferrannini E: Operation of Randle's cycle in patients with NIDDM. Diabetes 39: 383-389, 1990.
73. Garland PB and Randle PJ: Regulation of glucose uptake by muscle: effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J 93: 678-687, 1964.
74. Garland PB, Newshokne EA, and Randle PJ: Regulation of glucose uptake by muscle: effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and lactate/pyruvate and L-glycerol-3-phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem J 93: 665-678, 1964.
75. Kruszynska YT, McCormack JG, and Melntyre N: Effect of non-esterified fatty acid availability on insulin stimulated glucose utilisation and tissue pyruvate dehydrogenase activity in the rat. Diabetologia 33: 396-402, 1990.
76. Vaag AA, Handberg A, Skött P, Richter EA, and Beck-Nielsen H: Glucose-fatty acid cycle operates in humans at the levels of both whole body and skeletal muscle during low and high physiological plasma insulin concentrations. Eur J Endocrinol 130: 70-79, 1994.
77. Hissin PJ, Karnieli E, Simpson A, Salans LB, and Cushman SW: A possible mechanism of insulin resistance in the rat adipose cell with high fat/low carbohydrate feeding. Diabetes 31: 589-592, 1982.
78. Grundleger M and Thenen S: Decreased insulin binding, glucose transport, and glucose metabolism in soleus muscle of rats fed a high fat diet. Diabetes 31: 232-237, 1982.
79. Dohm GL, Tapscott EB, Pories WJ, Dabbs DJ, Flickinger EG, Meelheim D, Fushiki T, Atkinson SM, Elton CV, and Caro JF: An in vitro human muscle preparation suitable for metabolic studies: decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest 82: 486-494, 1988.
80. Handberg A, Vaag A, Beck-Nielsen H, and Vinten J: Peripheral glucose uptake and skeletal muscle GLUT4 content in man: effect of insulin and free fatty acids. Diabetic Med 9: 605-610, 1992.
81. Wititsuwannakul D and Kim K: Mechanism of palmityl coenzyme: an inhibition of liver glycogen synthase. J Biol Chem 252: 7812-7817, 1977.
82. Nuttall FQ, Cannon MC, Bai G, and Lee EY: Primary structure of human liver glycogen synthase deduced by cDNA cloning. Arch Biochem Biophys 311: 443-449, 1994.
83. Orho M, Nikula-ljäs P, Schalin-Jäntti C, Permutt MA, and Groop LC: Isolation and characterization of the human muscle glycogen synthase gene. Diabetes 44: 1099-1105, 1995.
84. Larner J: Insulin and the stimulation of glycogen synthesis: the road from glycogen structure to glycogen synthase to cyclic AMP-dependent protein kinase to insulin mediators. In Advances in Enzymology and Related Areas of Molecular Biology, Meister A (Ed), Wiley, New York, 1990, pp 173-231.
85. Bonadonna RC, Saccomani MP, and Cobelli C: In vivo glucose transport in human skeletal muscle: tools, problems and perspectives. Bailliére's Clin Endocrinol Metab 7: 929-960, 1993.
86. Ginsberg RH, Browan TJ, Simon I, and Spector AA: Effect of the membrane lipid environment on the properties of insulin receptors. Diabetes 30: 773-780, 1981.
87. Storlien LH, Jenkins AB, Crisholm DJ, Pascoe WS, Khouri S, and Kraegen EW: Influence of dietary fat composition on the development of insulin resistance in rats. Diabetes 40: 280-289, 1991.
88. Williamson JR, Kreisberg RA, and Felts PW: Mechanism for the stimulation of gluconeogenesis in the rat. Proc Natl Acad Sci USA 56: 247-254, 1966.
89. Williamson JR, Browning T, and Scholz R: Control mechanisms of gluconeogenesis and ketogenesis. 1. Effects of oleate on gluconeogenesis in perfused rat liver. J Biol Chem 244: 4607-4616, 1969.
90. Struck E, Ashmore J, and Wieland O: Effects of glucagon and long chain fatty acids on glucose production by isolated perfused rat liver. Adv Enzyme Regul 4: 219-224, 1966.
91. Herrera MG, Kamm D, Ruderman N, and Cahill GF: Non-hormonal factors in the control of gluconeogenesis. Adv Enzyme Regul 4: 225-235, 1966.
92. Friedman B, Goodman EH Jr, and Weinhouse S: Effects of insulin and fatty acids on gluconeogenesis in the rat. J Biol Chem 242: 3620-3627, 1967.
93. Blumenthal SA: Stimulation of gluconeogenesis by palmitic acid in rat hepatocytes: evidence that this effect can be dissociated from the provision of reducing equivalents. Metabolism 32: 971-976, 1983.
94. Exton JH, Corbin JG, and Park CR: Control of gluconeogenesis in liver. IV. Differential effects of fatty acids and glucagon on ketogenesis and gluconeogenesis in the perfused rat liver. J Biol Chem 244: 4095-4102, 1969.
95. Shaw JH and Wolfe RR: Glucose production in the perfused dog liver: effect of free fatty acids, and ketones. J Surg Res 37: 437-442, 1984.
96. Wolfe RR and Shaw JH: Inhibitory effect of plasma free fatty acids on glucose production in the conscious dog. Am J Physiol 246: E181-E186, 1984.
97. Clore JN, Glickman PS, Helm ST, Nestler JE, and Blackard WG: Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men. Diabetes 40: 1033-1040, 1991.
98. Johnston P, Hollenbeck C, Sheu W, Chen Y-DI, and Reaven GM: Acute changes in plasma non-esterified fatty acid concentration do not change hepatic glucose production in people with type 2 diabetes. Diabetic Med 7: 871-875, 1990.
99. Saloranta C, Taskinen MR, Widén E, Härkönen M, Melander A, and Groop LC: Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM. Diabetes 42: 1559-1566, 1993.
100. Puhakainen I and Yki-Järvinen H: Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM. Diabetes 42: 1694-1699, 1993.
101. Jenssen T, Nurjhan N, Consoli A, and Gerich JE: Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans: demonstration of hepatic auto-regulation without a change in plasma glucose concentration. J Clin Invest 86: 489-497, 1990.
102. Kubota M, Virkamäki A, and Yki-Järvinen H: Ethanol stimulates glycogenolysis in livers from fed rats. Proc Soc Exp Biol Med 201: 114-118, 1992.
103. Bevilacqua S, Bonadonna RC, Boni C, Ciociaro D, Maccari F, Gioricq MA, and Ferrannini E: Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism 36: 502-506, 1987.
104. DeFronzo RA, Deibert D, Hendler R, and Felig P: Insulin sensitivity and insulin binding to monocytes in maturity-onset diabetics. J Clin Invest 63: 939-946, 1979.
105. Kolterman OG, Gray RS, Griffin J, Burstein P, Insel J, Scarlett JA, and Olefsky JM: Receptor and postreceptor defects contribute to the insulin resistance in non-insulin-dependent diabetes mellitus. J Clin Invest 68: 957-969, 1981.
106. Greenfield MS, Doberne L, Kramer F, Tobey T, and Reaven G: Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes 31: 387-392, 1981.
107. DeFronzo RA, Simonsson D, and Ferrannini E: Hepatic and peripheral insulin resistance: a common feature in non-insulin-dependent diabetes. Diabetologia 23: 313-319, 1982.
108. Kimmerling G, Javorski WC, Olefsky JM, and Reaven GM: Locating the site(s) of insulin resistance in patients with non-ketotic diabetes mellitus. Diabetes 25: 673-678, 1976.
109. Golay A, DeFronzo RA, Ferrannini E, Simonson DC, Thorin D, Acheson K, Thiébaud D, Curchod B, Jéquier E, and Felber JP: Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients. Diabetologia 31: 585-591, 1988.
110. Bierman EL, Dole VP, and Roberts TN: An abnormality of non-esterified fatty acid metabolism in diabetes mellitus. Diabetes 6: 475-479, 1957.
111. Reitsma WD: The relationship between serum free fatty acids and blood sugar in non-obese and obese diabetics. Acta Med Scand 182: 353-361, 1967.
112. Howard BV, Savage PJ, Nagulesparan M, Bennion LJ, Unger RH, and Bennett PH: Evidence for marked sensitivity to the antilipolytic action of insulin in obese maturity-onset diabetics. Metabolism 28: 744-750, 1979.
113. Fraze E, Dormer CC, Swislocki ALM, Chiou Y-A, Chen Y-D, and Reaven GM: Ambient plasma free fatty acid concentrations in non-insulin-dependent diabetes mellitus: evidence for insulin resistance. J Clin Endoorinol Metab 61: 807-811, 1985.
114. Golay A, Swislocki ALM, Chen Y-D, and Reaven GM: Relationships between free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals. Metab Clin Exp 36: 692-696, 1987.
115. Chen Y-I, Golay A, Swislocki ALM, and Reaven GM: Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 64: 17-21, 1987.
116. Bolzano K, Sandhofer F, Sailer S, and Braunsteiner J: The effect of oral administration of sucrose on the turnover rate of plasma free fatty acids and on the esterification rate of plasma free fatty acids to plasma triglycerides in normal subjects, patients with primary endogenous hypertriglyceridemia, and patients with well controlled diabetes mellitus. Harm Metab Res 4: 439-446, 1972.
117. Taskinen M-R, Bogardus C, Kennedy A, and Howard BV: Multiple disturbances of free fatty acid metabolism in non-insulin-dependent diabetes: effect of oral hypoglycemic therapy. J Clin Invest 76: 637-644, 1985.
118. Reaven GM, Hollenbeck C, Jeng C-Y, Wu MS, and Chen Y-I: Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 37: 1020-1024, 1988.
119. Arner P, Bolinder J, Engfeldt P, and Östman J: The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyper-insulinemia, and starvation. Metabolism 30: 753-760, 1981.
120. Lonnroth P, Digirolamo M, Krotkiewski M, and Smith U: Insulin binding and responsiveness in fat cells from patients with reduced glucose tolerance and type II diabetes. Diabetes 32: 748-754, 1983.
121. Yki-Järvinen H, and Taskinen M-R: Inter-relationships among insulin's antilipolytic and glucoregulatory effects and plasma triglycerides in nondiabetic and diabetic patients with endogenous hypertriglyceridemia. Diabetes 37: 1271-1278, 1988.
122. Nurjhan N, Consoli A, and Gerich J: Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus. J Clin Invest 89: 169-175, 1992.
123. Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widén E, Schalin C, and Groop L: Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 32: 337-343, 1989.
124. Vaag A, Henriksen JE, and Beck-Nielsen H: Decreased insulin activation of glycogen synthase in skeletal muscles in young non-obese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 89: 782-788, 1992.
125. Schalin-Jäntti C, Härkönen M, and Groop L: Impaired activation of glycogen synthase in people at increased risk for developing NIDDM. Diabetes 41: 598-604, 1992.
126. Gulli G, Ferrannini E, Stern M, Haffner S, and DeFronzo RA: The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents. Diabetes 41: 1575-1586, 1992.
127. Rabinovitz D and Zierler KL: Forearm metabolism in obesity and its response to intra-arterial insulin. J Clin Invest 41: 2173, 1962.
128. DeFronzo RA, Soman V, Sherwin RS, Hendler R, and Felig P: Insulin binding to monocytes and insulin action in human obesity, starvation and refeeding. J Clin Invest: 204-213, 1978.
129. Kolterman OG, Insel J, Saekow M, and Olefsky JO: Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. J Clin Invest 65: 1272, 1980.
130. Bogafdus C, Lillioja S, Mott D, Reaven GM, Kashiwagi A, and Foley JE: Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians. J Clin Invest 73: 800-805, 1984.
131. Hollenbeck CB, Chen Y-DI, and Reaven GM: A comparison of the relative effects of obesity and non-insulin-dependent diabetes mellitus on in vivo stimulated glucose utilization. Diabetes 33: 622-626, 1984.
132. Bonadonna RC, Groop LC, Kraemer N, Ferrannini E, DelPrato S, and DeFronzo RA: Obesity and insulin resistance in humans: a dose response study. Metabolism 39: 452-459, 1990.
133. Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferrannini E, and DeFronzo RA: The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 72: 96-107, 1991.
134. Groop LC, Bonadonna RC, Simonson DC, Petrides AS, Shank M, and DeFronzo RA: Effect of insulin on oxidative and non-oxidative pathways of free fatty acid metabolism in human obesity. Am J Physiol 263: E79-E84, 1992.
135. Campbell PJ, Mandarine LJ, and Gerich JE: Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. Metabolism 37: 15-21, 1988.
136. Kashiwagi A, Bogardus C, and Lillioja S: In vitro insensitivity of glucose transport and antilipolysis to insulin due to receptor and postreceptor abnormalities in obese Pima Indians with normal glucose tolerance. Metabolism 33: 772-777, 1984.
137. Golay A, Swislocki ALM, Chen Y-DI, Jaspan JB, and Reaven GM: Effect of obesity on ambient plasma glucose, insulin, growth hormone, and glucagon concentrations. J Clin Endocrinol Metab 63: 481-484, 1986.
138. Howard BV, Klimes I, Vasques B, Brady D, Nagulesparan M, and Unger RH: The antilipolytic action of insulin in obese subjects with resistance to its glucoregulatory action. J Clin Endocrinol Metab 58: 544-548, 1984.
139. Malmendier CL, Delcroix C, and Berman M: Interrelations in the oxidative metabolism of free fatty acids, glucose and glycerol in normal and hypejrlipemic patients. J Clin Invest 54: 461-476, 1974.
140. Kissebah AH, Alfarsi S, Adams PW, and Wynn V: Role of insulin resistance in adipose tissue and liver in the pathogenesis of endogenous hypertriglyceridemia in man. Diabetologia 12: 563-571, 1976.
141. Kissebah AH, Alfarsi S, Adams PW, Seed M, Folkard J, and Wynn V: Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridemia: effects of 2,3-dimethyl,5(2,5-xyloxy)valeric acid therapy. Atherosclerosis 24: 199-218, 1976.
142. Nikkilä EA, and Taskinen M-R: Hypertriglyceridemia and insulin secretion: a complex casual relationship. In Atherosclerosis II, Jones JR (Ed), Springer-Verlag, Berlin, 1970, pp 220-230.
143. Steiner G, Morita S, and Vranic M: Resistance to insulin but not to glucagon in lean human hypertriglyceridemics. Diabetes 29: 899-905, 1980.
144. Reaven GM, Mejean L, Villaume C, Drouin P, and Debry G: Plasma glucose and insulin responses to oral glucose in non-obese subjects and patients with endogenous hypertriglyceridemia. Metabolism 32: 447-450, 1983.
145. Widén E, Ekstrand A, Saloranta C, Franssila-Kallunki A, Eriksson J, Schalin-Jäntti C, and Groop L: Insulin resistance in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 35: 1140-1145, 1992.
146. Saloranta C, Groop L, Ekstrand A, Franssila-Kallunki A, and Taskinen M-R: The effect of an antilipolytic agent (acipimox) on the insulin resistance of lipid and glucose metabolism in hypertriglyceridaemic patients. Acta Diabetol 31: 6-13, 1994.
147. Shen D-C, Fuh MTT, Shieh S-M, Chen Y-D, and Reaven GM: Effect of gemfibrozil treatment in sulfonylurea-treated patients with non-insulin-dependent diabetes mellitus. J Endocrinol Metab 73: 503-510, 1991.
148. Vuorinen-Markkola H, Yki-Järvinen H, and Taskinen M-R: Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36: 161-169, 1993.
149. Franssila-Kallunki A, Rissanen A, Ekstrand A, Ollus A, and Groop LC: Effects of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity in obese individuals. Am J Clin Nutr 55: 356-361, 1992.
150. Tanaka K and Ikeda Y: Hypoglycin and Jamaican vomiting sickness. Fatty Acid Oxidation: Clinical Biochemical and Molecular Aspects Tanaka K and Coates PM (Eds), Alan R Liss, New York, 167-184, 1990.
151. Kean EA: Selective inhibition of acyl-CoA dehydrogenases by a metabolite of hypoglycin. Biochim Biophys Acta 422: 8-14, 1976.
152. Billington D, Osmundsen H, Stanley H, and Sherrat HSA: Mechanisms of the metabolic disturbances caused by hypoglycin and by pent-4-enoic acid in vitro studies. Biochem Pharmacol 27: 2879-2890, 1978.
153. Sabbach E, Cuebas D, and Schulz H:3-Mercaptopropionic acid, a potent inhibitor of fatty acid oxidation in rat mitochondria. J Biol Chem 260: 7337-7342, 1985.
154. Melde K, Buettner H, Boschert W, Wolf HOP, and Ghisla S: Mechanism of hypoglycemic action of methylenecyclopropylglycine. Biochem J 259: 921-924, 1989.
155. Tutwiler GF, Kirsch T, Mohrbacher RJ, and Ho W: Pharmacologie profile of methyl-2-tetradecylglycidate (McN-3716): an orally effective hypoglycemic agent. Metabolism 27: 1539-1556, 1978.
156. Mandarine L, Tsalikian E, Barthold S, Marsh H, Carney A, Buerklin E, Tutwiler G, Haymond M, Handwerger B, and Rizza R: Mechanism of hyperglycemia and response to treatment with an inhibitor of fatty acid oxidation in a patient with insulin resistance due to antiinsulin receptor antibodies. J Clin Endocrinol Metab 59: 658-664, 1984.
157. Wolf HPO: Aryl-substituted 2-oxirane carboxylic acids: a new group of antidiabetic drugs. In New Antidiabetic Drugs, Bailey CJ and Flatt PR (Eds), Smith-Gordon, London, 1990, pp 217-229.
158. Ratheiser K, Schneeweiss B, Waldhausl W, Fasching P, Korn A, Nowotny P, Rohac M, and Wolf HPO: Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus. Metabolism 40: 1185-1190, 1991.
159. Young DA, Ho RS, Bell PA, Cohen DK, McIntosh RH, Navelson J, and Foley JE: Inhibition of hepatic glucose production by SDZ 51641. Diabetes 39: 1408-1413, 1990.
160. Taskinen MR and Nikkilä EA: Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia. Atherosclerosis 69: 249-255, 1988.
161. Carlson LA and Ostman J: Inhibition of the mobilization of free fatty acids from adipose tissue in diabetes. II. Effect of nicotinic acid and acetylsalicylate on blood glucose in human diabetics. Acta Med Scand 178: 71-79, 1965.
162. Stowers JM, Bewsher PD, Stein JM, and Mowat J: Studies on the effects of nicotinic acid given orally or intravenously on an oral and intravenous glucose tolerance in man. In Metabolic Effects of Nicotinic Acid and its Derivatives, Gey KF and Carlson LA (Eds), Huber, Bern, 1970, pp 723-731.
163. Gurian H and Adlersberg D: The effect of large doses of nicotinic acid on circulating lipids and carbohydrate tolerance. Am J Med Sci 237: 12, 1959.
164. Miettinen TA, Taskinen M-R, Pelkonen R, and Nikkilä EA: Glucose tolerance and plasma insulin in man during acute and chronic administration of nicotinic acid. Acta Med Scand 186: 247-253, 1969.
165. Belle M and Halpern MM: Oral nicotinic acid for hyperlipemia: with emphasis on side effects. Am J Cardiol 2: 449, 1958.
166. Molnar GD, Berge KG, Rosevear JW, McGuckin WF, and Achor RWP: The effect of nicotinic acid in diabetes mellitus. Metabolism 13: 181-189, 1964.
167. Garg A and Grundy SM: Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 264: 723-726, 1990.
168. Kahn SE, Beard JC, Schwartz MW, Ward WK, Ding HL, Bergman RN, Taborsky GJ, and Porte DJ: Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 38: 562-658, 1989.
169. Fuccella LM, Goldaniga G, Lovisolo P, Maggi E, Musatti L, Mandelli V, and Sirtori CR: Inhibition of lipolysis by nicotinic acid and by acipimox. Clin Pharmacol Ther 28: 790-795, 1980.
170. Lovisolo PP, Briatico-Vangosa G, Orsini G, Ronchi R, Angelucci R, and Valzelli G: Pharmacological profile of a new anti-lipolytic agent:5-methyl-pyrazine-2-carboxylic acid-4-oxide (Acipimox). I. Mechanisms of action. Pharmacol Res Commun 13: 151-161, 1981.
171. Fulcher GR, Farrer M, Thow JC, Johnson AB, Davis SN, Miller M, Orskov H, and Alberti KGMM: The glucose-fatty acid cycle in non-insulin-dependent diabetes mellitus: the acute effects of inhibition of lipolysis overnight with acipimox. Diabetes Nutr Metab 4: 285-293, 1990.
172. Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen M-R, and Groop LC: Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34: 409-415, 1991.
173. Vaag AA, Skött P, Damsbo P, Gall M-A, Richter EA, and Beck-Nielsen H: Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 88: 1282-1290, 1991.
174. Ekstrand A, Saloranta C, Ahonen J, Grönhagen-Riska C, and Groop L: Reversal of steroid-induced insulin resistance by a nicotinic acid derivative in man. Metabolism 41: 692-697,1992.
175. Saloranta C, Groop L, Ekstrand A, Franssila-Kallunki A, Eriksson J, and Taskinen M-R: Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes. Diabetic Med 10: 950-957, 1993.
176. Fulcher GR, Walker M, Catalano C, Agius L, and Alberti KGMM: Metabolic effects of suppression of non-esterified fatty acid levels with acipimox in obese NIDDM subjects. Diabetes 41: 1400-1408, 1992.
177. Walker M, Agius L, Örskov H, and Alberti KGMM: Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids. Metabolism 42: 601-608, 1993.
178. Fulcher GR, Walker M, Catalane C, Farrer M, and Alberti KGMM: Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox. Clin Sci 82: 565-571, 1992.
179. Fulcher GR, Walker M, Farrer M, Johnson AS, and Alberti KGMM: Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate. Metabolism 42: 308-314, 1993.
180. Nagasaka Y, Kaku K, Nakamura K, and Kaneko T: cAMP inhibits the insulin-stimulated mitogen-activated protein kinase pathway in rat hepatoma H4EII cells. Biochem Biophys Res Commun 202: 1104-1112, 1994.
181. Dulbecco A, Albenga C, Boretta G, Vacca G, Milanesi G, and Lavezzari M: Effect of acipimox on plasma glucose levels in patients with non-insulin-dependent diabetes mellitus. Curr Ther Res 46: 478-483, 1989.
182. Dean JD, McCarthy S, Betteridge DJ, Whately-Smith C, Powell J, and Owens DR: The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia. Diabetic Med 9: 611-615, 1992.
183. Fulcher GR, Catalano C, Walker M, Farrer M, Thow J, Whately-Smith CR, and Alberti KGMM: A double blind study of the efefct of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus. Diabetic Med 9: 908-914, 1992.
184. Vaag AA and Beck-Nielsen H: Effects of prolonged acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. Acta Endocrinol 127: 344-350, 1992.
185. Worm D, Henriksen JE, Vaag A, Thye-Rönn P, Melander A, and Beck-Nielsen H: Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period. J Clin Endocrinol Metab 78: 717-721, 1994.
186. Irie M, Sakuma T, Tsushima T, Shizume K, and Nakao K: Effect of nicotinic acid administration on plasma growth hormone concentrations. Proc Soc Exp Biol Med 126: 708-711, 1967.
187. Boyle PJ, Avogaro A, Smith L, Bier DM, Pappu AS, Illingworth DR, and Cryer PE: Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans. Am J Physiol 263: E168-E172, 1992.