Novel therapeutic strategies for the treatment of Type 2 diabetes

Diabetes/Metabolism Reviews

Volumn 14, Issue 3, 1998, Pages 207-225

  Perfetti, Riccardo ^a,b   Barnett, Philip S ^a,b   Mathur, Ruchi ^a   Egan, Josephine M ^c  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Insulin resistance; Novel therapies; Type 2 diabetes

Indexed keywords

1,1 DIMETHYL 2 (2 MORPHOLINOPHENYL)GUANIDINE FUMARATE; 2 METHOXY 4 [2 [2 (3,5 DIMETHYL 1 PIPERIDINYL)NICOTINAMIDO]ETHYL]BENZOIC ACID; ACARBOSE; AD 5075; ANTIDIABETIC AGENT; CHROMIUM PICOLINATE; CIGLITAZONE; EMIGLITATE; ENGLITAZONE; ETOMOXIR; GLIMEPIRIDE; GLIQUIDONE; GLUCAGON LIKE PEPTIDE; MIGLITOL; MITIGLINIDE; MOLYBDENUM; NATEGLINIDE; NEW DRUG; NN 623; PIOGLITAZONE; PRAMLINTIDE; REPAGLINIDE; ROSIGLITAZONE; SELENIUM; SULFONYLUREA DERIVATIVE; TROGLITAZONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANADIC ACID; VOGLIBOSE; ZINC;

CARDIOVASCULAR DISEASE; DIABETES CONTROL; DIABETIC MICROANGIOPATHY; DIABETIC NEUROPATHY; HUMAN; HYPERGLYCEMIA; METABOLIC REGULATION; MICROANGIOPATHY; NEUROPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; REVIEW;

ANIMALS; DIABETES MELLITUS, TYPE 2; DIET; EXERCISE; HUMANS; HYPOGLYCEMIC AGENTS; LIFE STYLE; WEIGHT LOSS;

EID: 0031740403     PISSN: 07424221     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-0895(1998090)14:3<207::AID-DMR214>3.0.CO;2-J     Document Type: Review

References (126)

1. LeRoith D, Taylor SI, and Olefsky JM: Diabetes Mellitus. Lippincott-Raven, Philadelphia, 1996.
2. American Diabetes Association: Clinical Practice Recommendations. Diabetes Care 19 (Suppl 1): S1-S117, 1996.
3. Golberg RB, Holvey SM, and Schneider JA: Dose-response study of glimepiride in patients with NIDDM who have previously received sulfonylurea agents. The glimepiride protocol: 201 study group. Diabetes Care 19: 849-856, 1996.
4. Smits P, and Thien T: Cardiovascular effects of sulphonylurea derivatives: implications for the treatment of NIDDM? Diabetologia 38: 116-121, 1995.
5. Muller G, Satoh Y, and Geisen K: Extrapancreatic effects of sulfonylureas: a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract 28 (Suppl): S115-S137, 1995.
6. Rosskamp R, Wernicke-Panten K, and Draeger E: Clinical profile of the novel sulphonylurea glimepiride. Diabetes Res Clin Pract 31 (Suppl): S33-S42, 1996.
7. Pogatsa G: What kind of cardiovascular alterations could be influenced positively by oral antidiabetic agents? Diabetes Res Clin Pract 31 (Suppl): S27-S31, 1996.
8. Nicolai H, Brickl R, Eschey H, Greischel A, Heinzel G, Konig E, Limmer J, and Rupprecht E: Duration of action and pharmacokinetics of the oral antidiabetic drug gliquidone in patients with non-insulin-dependent (type 2) diabetes mellitus. Arzneimittel-Forsch 47: 247-252, 1997.
9. Gregorio F, Ambrosi F, Filipponi P, Cristallini S, and Santeusanio F: Glucose modulates the amount, but not the kinetics, of insulin release by sulphonylureas. J Diabetes Complic 8: 204-212, 1994.
10. Harrower AD: Pharmacokinetics of oral antihyperglycemic agents in patients with renal insufficiency. Clin Pharmacokinet 31: 111-119, 1996.
11. Malaisse WJ: Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family. Horm Metab Res 27(6): 263-266, 1995.
12. Wolffenbuttel BHR, and Graal MB: New treatments for patients with type 2 diabetes mellitus. Postgrad Med J 72: 657-662, 1996.
13. Bakkali Nadi A, Zhang TM, and Malaisse WJ. Effects of the methyl esters of pyruvate, succinate and glutamate on the secretory response tomeglitinide analogues in rat pancreatic islets. Pharmacol Res 33: 191-194, 1996.
14. Vinambres C, Villanueva-Penarillo ML, Valverde I, and Malaisse WJ: Repaglinide preserves nutrient-stimulated biosynthetic activity in rat pancreatic islets. Pharmacol Res 34: 83-85, 1996.
15. Nakashima E, Nakamura J, Koh N, Sakakibara F, Hamada Y, and Hotta N: Effect of a novel hypoglycemic agent, KAD-1229 on glucose metabolism and fructose-2,6-bisphosphate content in isolated hepatocytes of normal rats. Diabetes Res Clin Pract 34(1): 13-22, 1996.
16. Ohnota H, Koizumi T, Tsutsumi N, Kobayashi M, Inoue S, and Sato F: Novel rapid- and short-acting hypoglycemic agent, a calcium (2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) that acts on the sulfonylurea receptor: comparison of effects between KAD-1229 and gliclazide. J Pharmacol Exp Ther 269(2): 489-495, 1994.
17. Rabuazzo AM, Buscema M, Vicini C, Caltabiano V, Vetri M, Forte F, Vigneri R, and Purrello F: Glyburide and tolbutamide induce desensitization of insulin release in rat pancreatic islets by different mechanisms. Endocrinology 131: 1825-1820, 1992.
18. Davalli AM, Pontiroli AE, Socci G, Bertuzzi F, Fattori B, Braghi S, Carlo VD, and Pozza G: Human islets chronically exposed in vitro to different stimuli become unresponsive to the same stimuli given acutely: evidence supporting specific desensitization rather than beta-cell exhaustion. J Clin Endocrinol Metab 74: 790-794, 1992.
19. Skillman CA, and Raskin P: A double-masked placebo-controlled trial assessing effects of various doses of BTS 67 582, a novel insulinotropic agent, on fasting hyperglycemia in NIDDM patients. Diabetes Care 20: 591-596, 1997.
20. Dunne MJ, Kane C, Harding EA, Jaggar JH, Jones RB, and Ashcroft SJH: BTS 67582 a novel insulin releasing agent (Abstract). Diabetic Med 12 (Suppl 1): S31-S32, 1995.
21. Ikenoue T, Okazaki K, Fujitani S, Tsuchiya Y, Akiyoshi M, Maki T and Kondo N: Effect of a new hypoglycemic agent, A4166 [(-)-N(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclimide. Biol Pharm Bull 20: 354-359, 1997.
22. Akiyoshi M, Kakei M, Nakazaki M, and Tanaka H: A new hypoglycemic agent, A-4166, inhibits ATP-sensitive potassium channels in rat pancreatic beta-cells. Am J Physiol 268: E185-E193, 1995.
23. Kikuki M: Modulation of insulin secretion in non-insulin dependent diabetes mellitus by two novel oral hypoglycemic agents, NN623 and A4166. Diabetes Med 13 (9 Suppl 6): S151-S155, 1996.
24. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, and Creutzfeldt W: Preserved incretin activity of glucagon-like peptide-1 [7-36 amide] but not human gastric inhibitory polypeptide in patients with type 2 diabetes mellitus. J Clin Invest 91: 301-307, 1993.
25. Cooper GJ, and Tse CA: Amylin, amyloid and age related disease. Drugs Aging 9: 202-212, 1996.
26. Bell GI, Santerre RF, Mullenhach GT. Hamster preproglucagon contains the sequence of glucagon and related peptides. Nature 302: 716-718, 1983.
27. Holst JJ: Glucagon-like peptide-1 (GLP-1) a newly discovered GI hormone. Gastroenterology 107: 1048-1055, 1994.
28. Orsakov C: Glucagon-like peptide-1, a new hormone of the enteroinsular axis. Diabetologia 35: 701-711, 1992.
29. Nauck MA, Stockman R, Ebert R, and Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin dependent) diabetes. Diabetologia 29: 46-52, 1986.
30. Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W: Normalization of fasting hyperglycemia by exogenous glucagon-like peptide-1 [7-36 amide] in type 2 (non-insulin dependent) diabetic patients. Diabetologia 36: 741-744, 1993.
31. Tanizawa Y, Riggs AC, Elbein SC, Whelan A, Donis-Keller H, and Permutt MA: Human glucagon-like peptide-1 receptor gene in NIDDM: identification and use of simple sequence repeat polymorphism in genetic analysis. Diabetes 43: 752-757, 1994.
32. Zhang Y, Cook ITE, Hattersley AT, Firth R, Saker PI, Warren-Perry M, Stoffel M, and Turner RC: Non-linkage of the glucagon-like peptide-1 receptor gene with maturity onset diabetes of the young. Diabetologia 37: 721-724, 1994.
33. Gutniak M, Orskov C, Holst JJ, Ahren B, and Efandic S. Antidiabetic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and in patients with diabetes mellitus. N Engl J Med 326: 1316-1322, 1992.
34. Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, and Nauck MA: Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide (7-36) amide in type 1 diabetes. Diabetes Care 19: 580-586, 1996.
35. Wettergren A, Schjoldager B, Mortesen PE, Myhre J, Christiansen J, and Holst JJ. Truncated GLP-1 (proglucagon 78-107 amide) inhibits gastric and pancreatic function in man. Dig Dis Sci 38: 665-673, 1993.
36. Schirra J, Wank U, Houck P, Goke B, and Katcschinski M: Effects of GLP-1 on human antro-pyloroduodenal motility. Gastroenterology 110: A1116, 1996.
37. Willms B, Werner J, Holst P, Orskov C, Creutzfeldt W, and Nauch MA: Gastric emptying, glucose responses, and insulin secretion after a liquid meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (non-insulin-dependent) diabetic patients. J Clin Endocrinol Metab 81: 327-332, 1996.
38. Dupre J, Behne MT, Hramiak IM, McFurlane P, Williamson P, Zabel P, and McDonald TJ: Glucagon-like peptide-1 reduces postprandial glycemic excursion in IDDM. Diabetes 44: 626-630, 1995.
39. Ritzel R, Orskov C, Holst JJ, and Nauck M: Pharmacokinetic, insulinotropic and glucagonostatic properties of GLP-1 after subcutaneous injection in healthy volunteers: dose-response relationships. Diabetologia 38: 720-25, 1995.
40. Rauchman J, Barrow BA, Levy JC, and Turner RC: Near normalization of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia 40: 205-211, 1997.
41. Moyses C, Young A, and Kolterman O: Modulation of gastric emptying as a therapeutic approach to glycemic control. Diabetic Med 13: S34-S38, 1996.
42. Koltermann OG, Gottlieb A, Moyses C, and Colbum W: Reduction of postprandial hyperglycemia in subjects with IDDM by intravenous infusion of AC137, a human amylin analogue. Diabetes Care 18: 1179-1182, 1995.
43. Wolffenbuttel BH, and Graal MB: New treatment for patients with type 2 diabetes mellitus. Postgrad Med J 72: 657-662, 1996.
44. Bischoff H: The mechanism of alpha-glucosidase inhibition in the management of diabetes. Clin Invest Med 18: 303-311, 1995.
45. Coniff RF, Shapiro JA, Robbins D, Kleinfield R, Seaton TB, Beisswenger P, and McGill JB: Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM: a placebo-controlled dose-comparison study. Diabetes Care 12: 979-984, 1995.
46. Baron A, and Neumann C: Project interim results: a large multicentric study of patients with type II diabetes. Clin Ther 19: 282-294, 1997.
47. Lefebvre PJ and Scheen AJ: The use of acarbose in the prevention and treatment of hypoglycemia. Eur J Clin Invest 34 (Suppl 3): 36-39, 1994.
48. Reuser AJ and Wisselaar HA: An evaluation of the potential side effect of alpha glucosidase inhibitors used for the management of diabetes mellitus. Eur J Clin Invest 24: 19-24, 1994.
49. Sels JP, Kingma PJ, Wolffenbuttel BH, Menheere PP, Branolte JH, and Nieuwehuijzen Kruseman AC. Effect of miglitol (BAY m-1099) on fasting blood glucose in type 2 diabetes mellitus. Neth J Med 44: 198-201, 1994.
50. Sels JP, Nauta JJ, Menheere PP, Wolffenbuttel BH, and Nieuwenhuijzen Kruseman AC: Miglitol (Bay m 1099) has no extraintestinal effects on glucose control in healthy volunteers. Br J Clin Pharmacol 42: 503-506, 1996.
51. Tormo MA, Ropero MF, Nieto M, Martinez IM, and Campillo JE: In vitro study of the effect of miglitol on carbohydrate digestion and intestinal metabolism in normal and non-insulin-dependent diabetic rats. Can J Physiol Pharmacol 74: 1196-1203, 1996.
52. Pagano G, Marena S, Corgiat-Mansin L, Cravero F, Giorda C, Bozza M, and Rossi CM: Comparison of mignitol and glibenclimide in diet treated type 2 diabetic patients. Diabete Metab 21: 162-167, 1995.
53. Coniff R, and Krol A: Acarbose: a review of US clinical experience. Clin Ther 19: 16-26, 1997.
54. Shinozaki K, Suzuki M, Ikebuchi M, Hirose J, Hara Y, and Harano Y. Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in non diabetic hyperinsulinemic subjects. Metab Clin Exp 45: 731-737, 1996.
55. Goke B, Fuder H, Wiechorst G, Thiess U, Stridde E, Littke T, Kleist P, Arnold R, and Lucker PW. Voglibose (AO0128) is an efficient alpha-glucosidase inhibitor and mobilized the endogenous GLP-1 reserve. Digestion 56: 493-501, 1995.
56. Salehi A, and Lundquist I: Modulation of islet G-proteins, alpha-glucosidase inhibition and insulin release stimulated by various secretagogue. Biosci Rep 16: 23-34, 1996.
57. Lundquist I, Panagiotidis G, and Salehi A: Islet acid glucan-1,4-alpha-glucosidase: a putative key enzyme in nutrient stimulated insulin secretion. Endocrinology 137: 1219-1225, 1996.
58. Suter SL, Nolan JJ, Wallace P, Gumbiner B, and Olefsky JM. Metabolic effects of a new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care 15: 193-203, 1992.
59. Nolan JJ, Ludvik B, Ludvik M, Beerdsen P, Joyce M, and Olefsky JM: Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 331: 1188-1193, 1994.
60. Schwartz S, Raskin P, Fonseca V, and Graveline JF: Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. N Engl J Med 338: 861-866, 1998.
61. Antonucci T, Whitcomb R, McLain R, and Lockwood D: Impaired glucose tolerance is normalized by treatment with the thiazolidinedione troglitazone. Diabetes Care 20: 188-193, 1997.
62. Lee MK, Miles PDG, Khoursheed M, Gao KM, Mossa AR, and Olefsky JM: Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes 43: 1435-1439, 1994.
63. Bloomgarden ZT: American Diabetes Association Annual Meeting 1996: the etiology of type II diabetes, obesity, and the treatment of type II diabetes. Diabetes Care 19: 1311-1315, 1996.
64. Inzucchi SE, Maggs DG, Spollett GR, Page SL, Rife FS, Walton V, and Shulman GI: Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338: 867-872, 1998.
65. Dunaif A, Scott D, Finegood D, Quintana B, and Whitcomb R: The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 81: 3299-3306, 1996.
66. Imura H: A novel antidiabetic drug, troglitazone: reason for hope and concern. N Engl J Med 338: 908-909, 1998.
67. Shimabukuro M, Higa S, Shinzato T, Nagamine F, Komiya I, and Takasu N: Cardioprotective effects of troglitazone in streptozotocin-induced diabetic rats. Metab Clin Exp 45: 1168-1173, 1996.
68. Schoonjans K, Peidado-Onsbure J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, and Auwerx J: PPAR-alpha and PPAR-gamma activators direct a distinct tissue-specific transcriptional response via PPRE in the lipoprotein lipase gene. EMBO J 15: 5336-5348, 1996.
69. Berger J, Bailey P, Biswas C, Cullinan CA, Doebber TW, Hayes NS, Saperstein R, Smith RG, and Leibowitz MD: Thiazolidines produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology 137: 4189-4195, 1996.
70. Young PW, Cawthorne MA, Coyle PJ, Holder JC, Holman GD, Kozka IJ, Kirkham DM, Lister CA, and Smith SA: Repeat treatment of obese mice with BRL 49653, a new potent insulin sensitizer, enhances insulin action in white adipocytes: association with increased insulin binding and cell-surface GLUT-4 as measured by photoaffinity labeling. Diabetes 44: 1087-1092, 1995.
71. Berger J, Biswas C, Hayes N, Ventre J, Wu M, and Doebber TW: An antidiabetic thiazolidinedione potentates insulin stimulation of glycogen synthase in rat adipose tissue. Endocrinology 137: 1984-1990, 1996.
72. Matsuhisa M, Shi ZQ, Wan C, Lekas M, Rodgers CD, Giacca A, Kawamori R, and Vranic M. The effect of pioglitazone on hepatic glucose uptake measured with indirect and direct methods in alloxan-induced diabetic dogs. Diabetes 46: 224-231, 1997.
73. Fulgencio JP, Kohl C, Girard J, and Pegorier JP: Troglitazone inhibits fatty acid oxidation and esterification, and gluconeogenesis in isolated hepatocytes from starved rats. Diabetes 45: 1556-1562, 1996.
74. 2+ influx. J Endocrinol 150: 107-111, 1996.
75. Buchanan TA, Meehan WP, Jeng D, Chan TM, Nadler JL, Scott S, Rude RK, and Hsueh WA: Blood pressure lowering by pioglitazone: evidence for a direct vascular effect. J Clin Invest 96: 354-360, 1995.
76. Gimble JM, Robinson CE, Wu X, Kelly KA, Rodriguez BR, Kliewer SA, Lehmann JM, and Morris DC: Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol 50: 1087-1094, 1996.
77. Stevenson RW, McPerson RK, Person LM, Generoux PE, Swick AG, Spitzer J, Herbest JJ, Andrews KM, Kreutter DK, and Gibbs EM: The antihyperglycemic agent englitazone prevents the defect in glucose transport in rats fed a high-fat diet. Diabetes 45: 60-66, 1996.
78. Rowe IC, Lee K, Khan RN, and Ashford ML: Effect of englitazone on KATP and calcium-activated non-selective cation channels in CRI-G1 insulin secreting cells. Br J Pharmacol. 121: 531-539, 1997.
79. Pershadsingh HA, Szollosi J, Benson S, Hyun WC, Feuerestein BG, and Kurtz TW: Effects of ciglitiazone on blood pressure and intracellular calcium metabolism. Hypertension 21: 1020-1023, 1993.
80. Tsiani E, Abdullah N, and Fantus IG: Insulin-mimetic agents vanadate and pervanadate stimulate glucose but inhibit amino acid uptake. Am J Physiol 272: C156-C162, 1997.
81. Lyonette C, Martz D, and Martin A: L'emploitherapeutique de derives du vanadinium. Presse Med 191-192, 1899.
82. Goldfine AB, Simson DC, Folli F, Patti ME, and Kahn RC: In vitro and in vivo studies of vanadate in human and rodent diabetes mellitus. Mol Cell Biochem 153: 217-231, 1995.
83. McNeill JH, Yuen VG, Soter D, and Orving C: Increased potency of vanadinium using organic ligands. Mol Cell Biochem 153: 175-180, 1995.
84. Jackson T, Salhanick AI, Sparks JD, Sparks CE, Bolognino M, and Amatrude JM: Insulin-mimetic effects of vanadate in primary culture of rat hepatocytes. Diabetes 37: 1234-1240, 1988.
85. Duckworth WC, Solomon SS, Liepnieks J, Hamel FG, Hand S, and Peavy DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology 122: 2285-2289, 1988.
86. Shechter Y, and Karlish SJD. Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556-558, 1980.
87. Tamura S, Brown TA, Whipple JH, Fujita-Yamaguchi Y, Dubler RE, Chemg K, and Larner J: A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes. J Biol Chem 259: 6650-6658, 1984.
88. Schechter Y, and Ron A: Effect of depletion of bicarbonate or phosphate ions on insulin action in rat adipocytes: further characterization of the receptor-effector system. J Biol Chem 261: 14951-14954, 1986.
89. Degani H, Gochin M, Karlish SJD, and Schecter Y: Electron paramagnetic studies and insulin effects of vanadinium in rat adipocytes. Biochemistry 20: 5795-5799, 1981.
90. Werdan K, Bauridiel G, Fisher B, Krawietz W, Erdmann E, Schmitz W, and Scholtz H: Stimulatory and inhibitory action of vanadate on potassium uptake and cellular sodium and potassium in heart cells in culture. Biochim Biophys Acta 23: 79-83, 1982.
91. Shechter Y: Insulin mimetic effects of vanadate: possible implications for future treatments of diabetes. Diabetes 39: 1-5, 1990.
92. Fantus IG, Deragon G, Lai R, and Tang S: Modulation of insulin action by vanadate: evidence of a role for phosphotyrosine activity to alter cellular signaling. Mol Cell Biochem 153: 103-112, 1995.
93. Fantus IG, George R, Tang S, Chong P, and Poznansky MJ: The insulin-mimetic effect agent vanadate promotes receptor endocytosis and inhibits intracellular ligand-receptor degradation by a mechanism distinct from lysosomotropic agents. Diabetes 45: 1084-1093, 1996.
94. Malubu UH, Dryden SH, McCarthy D, Kilpatrick A, and Williams G: Effects of chronic vanadate administration in the STZ-induced diabetic rat. Diabetes 43: 9-15, 1994.
95. De Fronzo RA, Hendler R, and Simonson D: Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes 31: 795-801, 1982.
96. Domingo JL, Bosque MA, Luna M, and Corbella J: Prevention by Tyron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) of vanadate induced developmental toxicity in mice. Teratology 48: 133-138, 1993.
97. Li J, Elberg G, Gefel D, and Shechter Y: Permolybdate and pertungstate: potent stimulators of insulin effects in rat adipocytes: mechanism of action. Biochemistry 34: 6218-6225, 1995.
98. Matsumoto J: Vanadate, molybdate and tungstate for orthomolecular medicine. Med Hypoth 43: 177-182, 1994.
99. Barbera A, Fernandez-Alvarez J, Truc A, Gomis R, and Guinovart JJ: Effects of tungstate in neonatally streptozotocin-induced diabetic rats: mechanism leading to normalization of glycemia. Diabetologia 40: 143-149, 1997.
100. Fursinn C, Englisch R, Ebner K, Nowotny P, Volg C, and Waldhausl W: Insulin-like vs. non-insulin-like stimulation of glucose metabolism by vanadinium, tungstate and selenium compounds in rat muscle. Life Sci 59: 1989-2000, 1996.
101. Jonas JC, and Henquin JC: Possible involvement of a tyrosine kinase-dependent pathway in the regulation of phosphoinositide metabolism by vanadate in normal mouse islets. Biochem J 315: 49-55, 1996.
102. Barbera A, Rodriguez-Gil JE, and Guinovart JJ: Insulin-like actions of tungstate in diabetic rats: normalization of hepatic glucose metabolism. J Biol Chem 269: 20047-20053, 1994.
103. Anderson RA: Chromium and parental nutrition. Nutrition 11: 83-86, 1995.
104. Lee NA, and Reasner CA: Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 17: 1449-1452, 1994.
105. Haglund B, Ryckenberg K, Selenius O, and Dahlquist G: Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentrations of zinc. Diabetes Care 19: 873-875, 1996.
106. Sprietsma JE, and Schuitemaker GE: Diabetes can be prevented by reducing insulin production. Med Hypoth 42: 15-23, 1994.
107. Faure P, Roussel A, Coundray C, Richard MJ, Halimi S, and Favier A: Zinc and insulin sensitivity. Biol Trace Elements Res 32: 305-310, 1992.
108. Becker DJ, Reul B, Ozvelikay AT, Buchet JP, Henquin JC, and Brichard SM: Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats. Diabetologia 39: 3-11, 1996.
109. Ghosh R, Mukherjee B, and Chatterjee M: A novel effect of selenium on streptozotocin-induced diabetic mice. Diabetes Res 25: 165-171, 1994.
110. Eibl NL, Kopp HP, Nowak HR, Schnack CJ, Hopmier PG, and Schernthaner G: Hypomagnesemia in type II diabetes: effect of 3-month replacement therapy. Diabetes Care 18: 188-192, 1995.
111. Balon TW, Gu JL, Tokuyama Y, Jasman AP, and Nadler JL: Magnesium supplementation reduces development of diabetes in a rat model of spontaneous NIDDM. Am J Physiol 269: E745-E752, 1995.
112. Gorika F, Allegra A, Di Benedetto A, Giacobbe MS, Romano G, Cucinotta D, Buemi M, and Ceruso D: Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Magnesium Res 7: 43-47, 1994.
113. Coppack SW, Jensen MD, and Miles JM: In vivo regulation of lipolysis in humans. J Lipid Res 35: 177-193, 1994.
114. Foley JE: Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. Diabetes Care 15: 773-784, 1992.
115. Ginsberg BH: The role of technology in diabetes therapy. Diabetes Care 17 (Suppl 1): 51-55, 1994.
116. Zhou YP, Berggren PO, and Grill V: A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of beta-cell dysfunction in the obese diabetic db/db mouse. Diabetes 45: 580-586, 1996.
117. Bressler R, and Johnson D: New pharmacological approaches to therapy of NIDDM. Diabetes Care 15: 792-805, 1992.
118. Bahl JJ, Matsuda M, DeFronzo RA, and Bressler R: In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase. Biochim Pharmacol 53: 67-74, 1997.
119. Ammon HPT, Estler CJ, Heim F, and Okoronkwo B: Different effects on inhibition of lypolisis by nicotinic acid on the rate of glycolytic carbohydrate breakdown in brain and skeletal muscle. Life Sci 8: 213-221, 1969.
120. Molnar GD, Berge KG, Rosevear JW, McGuckin WF, and Anhon WP: The effect of nicotinic acid in diabetes mellitus. Metabolism 13: 181-190, 1964.
121. Lee KU, Park JY, Kim CH, Hong SK, Suh KI, Park KS, and Park SW: Effect of decreasing plasma free fatty acids by acipimox on hepatic glucose metabolism in normal rats. Metab Clin Exp 45: 1408-1414, 1996.
122. Christie AW, McCormick DK, Emmison N, Kraemer FB, Alberti KG, and Yeaman SJ: Mechanisms of anti-lipolytic action in isolated rat adipocytes. Diabetologia 39: 43-53, 1996.
123. Lefebvre PJ, and Scheen AJ: Improving the action of insulin. Clin Invest Med 18: 340-347, 1995.
124. DCCT (The Diabetes Control and Complementation Trial Group): The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977-986, 1993.
125. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S. Kojima Y, Furuyoshi N, and Shichiri M: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 28(2): 103-117, 1995.
126. McCarthy D, and Zimmet P: Diabetes 1994 to 2010: global estimates and projections. Leverkusen: Bayer AG 1-46, 1994.