Skip to main content
SpringerLink
Log in

PPAR-γ receptor agonists—a review of their role in diabetic management in Trinidad and Tobago

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The PPAR-γ receptor agonists, as a relatively new and perhaps still not very widely used class of antidiabetic agent in the Caribbean and particularly the Trinidadian context, possess pharmacologic properties that certainly have been shown to have impact on many of the inflammatory, metabolic, biochemical and structural macrovascular aberrations that occur in the type 2 diabetic. Activation of PPAR(gamma) nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. PPAR(gamma)-responsive genes also participate in the regulation of fatty acid metabolism, an important contributory pathogenic factor in this subset of patients. The unique mode of action of this class of therapeutic agent addresses a range of anomalies occurring at the cellular and sub-cellular level that are injurious to the diabetic. My aim in addressing the issue of the potential impact of PPAR-γ receptor agonists on cardiovascular disease (CVD) morbidity and mortality in the diabetic, is first, to seek to enhance both an awareness of, and greater familiarity among our own physicians, with this class of drug, and secondly, to effect a timely review of the recent literature as it relates to the tremendous possibilities for the potential clinical gains that might accrue from their use, in so far as this may serve to ameliorate the ravages of the CVD disease that all too tragically attends the type 2 diabetic, and more specifically those with the insulin resistance syndrome. (Mol Cell Biochem 263: 189–210, 2004)

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. PAHO: Health in The Americas, vol 2 (569), 1998, p 488

    Google Scholar 

  2. WHO: World Health Statistic Annual, July, 2001

  3. Beckles GL, Miller GJ, Kirkwood BR, Alexis SD, Carson DC, Byam NT: High total and cardiovascular disease mortality in adults of Indian descent in Trinidad, unexplained by major coronary risk factors. Lancet 1: 1298–1301, 1986

    Google Scholar 

  4. Miller GJ, Maude GH, Beckles GL: Incidence of hypertension and non-insulin dependent diabetes mellitus and associated risk factors in a rapidly developing Caribbean community: The St. James survey, Trinidad. J Epidemiol Community Health 50: 497–504, 1996

    Google Scholar 

  5. PAHO: Health in the Americas, vol 1, 1998, p 175

    Google Scholar 

  6. Chaturvedi N, Fuller JH: Ethnic differences in mortality from cardio-vascular disease in the UK: Do they persist in people with diabetes? J Epidemiol Community Health 50: 137–139, 1996

    Google Scholar 

  7. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM: Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84: 2329–2335, 1999

    Google Scholar 

  8. Seidell JC: Obesity, insulin resistance and diabetes—A worldwide epidemic. Br J Nutr 83(suppl 1): S5–S8, 2000

    Google Scholar 

  9. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S: The metabolically obese, normal-weight individual revisited. Diabetes 47: 699–713, 1998

    Google Scholar 

  10. Eriksson KF, Lindgarde F: Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study. Diabetologia 34: 891–898, 1991

    Google Scholar 

  11. Hughes VA, Fiatarone MA, Fielding RA, Kahn BB, Ferrara CM, Shepherd P, Fisher EC, Wolfe RR, Elahi D, Evans WJ: Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264: E855–E862, 1993

    Google Scholar 

  12. Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, de Ramon RA, Israel G, Dolezal JM: Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 222: 339–352; discussion 350–332, 1995

    Google Scholar 

  13. Hamilton BS, Paglia D, Kwan AY, Deitel M: Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1: 953–956, 1995

    Google Scholar 

  14. Kral JG: Morbidity of severe obesity. Surg Clin North Am 81: 1039–1061, 2001

    Google Scholar 

  15. Chagnon YC, Perusse L, Weisnagel SJ, Rankinen T, Bouchard C: The human obesity gene map: The 1999 update. Obes Res 8: 89–117, 2000

    Google Scholar 

  16. Naslund E, Hellstrom PM, Kral JG: The gut and food intake: An update for surgeons. J Gastrointest Surg 5: 556–567, 2001

    Google Scholar 

  17. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, Marks JA, Krakower GR, Jacob HJ, Weber J, Martin L, Blangero J, Comuzzie AG: Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97: 14478–14483, 2000

    Google Scholar 

  18. Smith SR: The endocrinology of obesity. Endocrinol Metab Clin North Am 25: 921–942, 1996

    Google Scholar 

  19. Flier JS: Clinical review 94: What's in a name? In search of leptin's physiologic role. J Clin Endocrinol Metab 83: 1407–1413, 1998

    Google Scholar 

  20. Flier JS: Leptin expression and action: New experimental paradigms. Proc Natl Acad Sci USA 94: 4242–4245, 1997

    Google Scholar 

  21. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS: Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nat Med 1: 1311–1314, 1995

    Google Scholar 

  22. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH: Lipotoxic heart disease in obese rats: Implications for human obesity. Proc Natl Acad Sci USA 97: 1784–1789, 2000

    Google Scholar 

  23. Hamer DH, Greenberg BD, Sabol SZ, Murphy DL: Role of the serotonin transporter gene in temperament and character. J Personal Disord 13: 312–327, 1999

    Google Scholar 

  24. Hu S, Brody CL, Fisher C, Gunzerath L, Nelson ML, Sabol SZ, Sirota LA, Marcus SE, Greenberg BD, Murphy DL, Hamer DH: Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior. Mol Psychiatr 5: 181–188, 2000

    Google Scholar 

  25. Weber RV, Stein DE, Scholes J, Kral JG: Obesity potentiates AOM-induced colon cancer. Dig Dis Sci 45: 890–895, 2000

    Google Scholar 

  26. Tchernof A, Starling RD, Turner A, Shuldiner AR, Walston JD, Silver K, Poehlman ET: Impaired capacity to lose visceral adipose tissue during weight reduction in obese postmenopausal women with the Trp 64 Arg beta3-adrenoceptor gene variant. Diabetes 49: 1709–1713, 2000

    Google Scholar 

  27. McFarlane-Anderson N, Bennett F, Wilks R, Howell S, Newsome C, Cruickshank K, Forrester T: The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women. Metabolism 47: 617–621, 1998

    Google Scholar 

  28. Hinney A, Schmidt A, Nottebom K, Heibult O, Becker I, Ziegler A, Gerber G, Sina M, Gorg T, Mayer H, Siegfried W, Fichter M, Remschmidt H, Hebebrand J: Several mutations in the melanocortin-4 re-ceptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab 84: 1483–1486, 1999

    Google Scholar 

  29. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79–83, 1999.

    Google Scholar 

  30. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K: cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose most abundant gene transcript 1). Biochem Biophys Res Commun 221: 286–289, 1996

    Google Scholar 

  31. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y: Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation 100: 2473–2476, 1999

    Google Scholar 

  32. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 409: 307–312, 2001

    Google Scholar 

  33. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF: Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98: 2005–2010, 2001

    Google Scholar 

  34. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen GL, Williams TD, Lewis H, Schafer AJ, Chatterjee VK, O'Rahilly S: Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402: 880–883, 1999

    Google Scholar 

  35. Dabelea D, Pettitt DJ, Hanson RL, Imperatore G, Bennett PH, Knowler WC: Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care 22: 944–950, 1999

    Google Scholar 

  36. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS: Brain dopamine and obesity. Lancet 357: 354–357, 2001

    Google Scholar 

  37. Schneider G, Kirschner MA, Berkowitz R, Ertel NH: Increased estro-gen production in obese men. J Clin Endocrinol Metab 48: 633–638, 1979

    Google Scholar 

  38. Ivandic A, Prpic-Krizevac I, Sucic M, Juric M: Hyperinsulinemia and sex hormones in healthy premenopausal women: Relative contribution of obesity, obesity type, and duration of obesity. Metabolism 47: 13–19, 1998

    Google Scholar 

  39. Lind L, Lithell H, Hvarfner A, Pollare T, Ljunghall S: On the relationships between mineral metabolism, obesity and fat distribution. Eur J Clin Invest 23: 307–310, 1993

    Google Scholar 

  40. Rosmond R, Lapidus L, Marin P, Bjorntorp P: Mental distress, obesity and body fat distribution in middle-aged men. Obes Res 4: 245–252, 1996

    Google Scholar 

  41. Cameron OG, Kronfol Z, Greden JF, Carroll BJ: Hypothalamic-pituitary-adrenocortical activity in patients with diabetes mellitus. Arch Gen Psychiatr 41: 1090–1095, 1984

    Google Scholar 

  42. Roy MS, Roy A, Brown S: Increased urinary-free cortisol outputs in diabetic patients. J Diabetes Complications 12: 24–27, 1998

    Google Scholar 

  43. Haffner SM, Karhapaa P, Mykkanen L, Laakso M: Insulin resistance, body fat distribution, and sex hormones in men. Diabetes 43: 212–219, 1994

    Google Scholar 

  44. Maes HH, Neale MC, Eaves LJ: Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27: 325–351, 1997

    Google Scholar 

  45. Ludwig DS, Peterson KE, Gortmaker SL: Relation between consumption of sugar-sweetened drinks and childhood obesity: A prospective, observational analysis. Lancet 357: 505–508, 2001

    Google Scholar 

  46. Nesto RW, Libby P: Diabetes Mellitus and Cardiovascular Disease. Braunwald, 2000, pp 2133–2150

  47. Tsai EC, Hirsch IB, Brunzell JD, Chait A: Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 43: 1010–1014, 1994

    Google Scholar 

  48. Stolar MW: Atherosclerosis in diabetes: The role of hyperinsulinemia. Metabolism 37: 1–9, 1988

    Google Scholar 

  49. Assmann G, Schulte H: The Prospective Cardiovascular Münster (PROCAM) study: Prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am Heart J 116: 1713–1724, 1988

    Google Scholar 

  50. Sprafka JM, Burke GL, Folsom AR, McGovern PG, Hahn LP: Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival. The Minnesota Heart Survey. Diabetes Care 14: 537–543, 1991

    Google Scholar 

  51. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339: 229–234, 1998

    Google Scholar 

  52. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med 335: 217–225, 1996

  53. Wilson PWF, Kannel WB: Epidemiology of hyperglycemia and atherosclerosis. In: N. Ruderman, J. Williamson, M. Brownlee (eds). Hyperglycemia, Diabetes, and Vascular Disease. Oxford University Press, Oxford, 1992, pp 21–29

    Google Scholar 

  54. Turner RC: The U.K. Prospective Diabetes Study. A review. Diabetes Care 21(suppl 3): C35–C38, 1998

    Google Scholar 

  55. Andersson DK, Svardsudd K: Long-term glycemic control relates to mortality in type II diabetes. Diabetes Care 18: 1534–1543, 1995

    Google Scholar 

  56. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352: 837–853, 1998

  57. Wingard DL, Barrett-Connor EL, Scheidt-Nave C, McPhillips JB: Prevalence of cardiovascular and renal complications in older adults with normal or impaired glucose tolerance or NIDDM. A population-based study. Diabetes Care 16: 1022–1025, 1993

    Google Scholar 

  58. Saltiel AR, Olefsky JM: Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 45: 1661–1669, 1996

    Google Scholar 

  59. Doustou JIM, Meyer C: Mechanisms by Which Rosiglitazone Improves Glycemic Control in Type 2 Diabetes Mellitus. Chicago, Illinois, 2001, abstract pp 2161

  60. Arner P: Free fatty acids—Do they play a central role in type 2 diabetes? Diabetes Obes Metab 3(suppl 1): S11–S19, 2001

    Google Scholar 

  61. Hellstrom L, Reynisdottir S, Langin D, Rossner S, Arner P: Regulation of lipolysis in fat cells of obese women during long-term hypocaloric diet. Int J Obes Relat Metab Disord 20: 745–752, 1996

    Google Scholar 

  62. Large V, Arner P: Regulation of lipolysis in humans. Pathophysiolog-ical modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab 24: 409–418, 1998

    Google Scholar 

  63. Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD: Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 37: 1020–1024, 1988

    Google Scholar 

  64. Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E: A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38: 1213–1217, 1995

    Google Scholar 

  65. Unger RH: Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 44: 863–870, 1995

    Google Scholar 

  66. Chen YD, Golay A, Swislocki AL, Reaven GM: Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 64: 17–21, 1987

    Google Scholar 

  67. Randle FJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1: 785–789, 1963

    Google Scholar 

  68. Exton JH, Corbin JG, 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

    Google Scholar 

  69. Bjorntorp P: Abdominal obesity and the development of noninsulin-dependent diabetes mellitus. Diabetes Metab Rev 4: 615–622, 1988

    Google Scholar 

  70. Stromblad G, Bjorntorp P: Reduced hepatic insulin clearance in rats with dietary-induced obesity. Metabolism 35: 323–327, 1986

    Google Scholar 

  71. Coppack SW, Jensen MD, Miles JM: In vivo regulation of lipolysis in humans. J Lipid Res 35: 177–193, 1994

    Google Scholar 

  72. Kissebah AH, Alfarsi S, Adams PW, Seed M, Folkard J, Wynn V: Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: Effects of 2,2-dimethyl, 5(2,5-xylyoxy) valeric acid therapy. Atherosclerosis 24: 199–218, 1976

    Google Scholar 

  73. Arner P: Regional adipocity in man. J Endocrinol 155: 191–192, 1997

    Google Scholar 

  74. Chen W, Yu Z, Li Y: The relationship between nonalcoholic fatty liver and insulin resistance with abnormal glucose metabolism. 8: 76–77, 2000

    Google Scholar 

  75. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N: Association of non-alcoholic fatty liver disease with insulin resistance. Am J Med 107: 450–455, 1999

    Google Scholar 

  76. Fonseca VA, Valiquett TR, Huang SM, Ghazzi MN, Whitcomb RW: Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: A randomized, controlled study. The Troglitazone Study Group. J Clin Endocrinol Metab 83: 3169–3176, 1998

    Google Scholar 

  77. Yamasaki Y, Kawamori R, Wasada T, Sato A, Omori Y, Eguchi H, Tominaga M, Sasaki H, Ikeda M, Kubota M, Ishida Y, Hozumi T, Baba S, Uehara M, Shichiri M, Kaneko T: Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan. Tohoku J Exp Med 183: 173–183, 1997

    Google Scholar 

  78. The Diabetic Coronary Patient. Science Press, 1999, p 80

  79. Khandoudi N, Delerive P: Rosiglitazone Protects the Diabetic Heart from Ischaemia Reperfusion Injury. Chicago, Illinois, 2001, abstract pp 478

  80. van Hoeven KH, Factor SM: A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease. Circulation 82: 848–855, 1990

    Google Scholar 

  81. Toyry JP, Niskanen LK, Mantysaari MJ, Lansimies EA, Uusitupa MI: Occurrence, predictors, and clinical significance of autonomic neuropathy in NIDDM. Ten-year follow-up from the diagnosis. Diabetes 45: 308–315, 1996

    Google Scholar 

  82. Nesto RW, Zarich S: Acute myocardial infarction in diabetes mellitus: Lessons learned from ACE inhibition. Circulation 97: 12–15, 1998

    Google Scholar 

  83. Jacoby RM, Nesto RW: Acute myocardial infarction in the diabetic patient: Pathophysiology, clinical course and prognosis. J Am Coll Cardiol 20: 736–744, 1992

    Google Scholar 

  84. Iwasaka T, Takahashi N, Nakamura S, Sugiura T, Tarumi N, Kimura Y, Okubo N, Taniguchi H, Matsui Y, Inada M: Residual left ventricular pump function after acute myocardial infarction in NIDDM patients. Diabetes Care 15: 1522–1526, 1992

    Google Scholar 

  85. Nahser PJ, Brown RE, Oskarsson H, Winniford MD, Rossen JD: Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation 91: 635–640, 1995

    Google Scholar 

  86. Abaci A, OŸuzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, Ergin A: Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 99: 2239–2242, 1999

    Google Scholar 

  87. Depre C, Vanoverschelde JL, Taegtmeyer H: Glucose for the heart. Circulation 99: 578–588, 1999

    Google Scholar 

  88. Bernardi L, Ricordi L, Lazzari P, Solda P, Calciati A, Ferrari MR, Vandea I, Finardi G, Fratino P: Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease. Circulation 86: 1443–1452, 1992

    Google Scholar 

  89. Zarich S, Waxman S, Freeman RT, Mittleman M, Hegarty P, Nesto RW: Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus. J Am Coll Cardiol 24: 956–962, 1994

    Google Scholar 

  90. Muller JE, Tofler GH, Stone PH: Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 79: 733–743, 1989

    Google Scholar 

  91. Gray RP, Yudkin JS, Patterson DL: Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: A role for plasminogen activator inhibitor? Br Heart J 70: 530–536, 1993

    Google Scholar 

  92. Gray RP, Patterson DL, Yudkin JS: Plasminogen activator inhibitor activity in diabetic and nondiabetic survivors of myocardial infarction. Arterioscler Thromb 13: 415–420, 1993

    Google Scholar 

  93. Colwell JA: Aspirin therapy in diabetes. Diabetes Care 20: 1767–1771, 1997

    Google Scholar 

  94. Aspirin therapy in diabetes. American Diabetes Association. Diabetes Care 20: 1772–1773, 1997

    Google Scholar 

  95. Weissberg P: Understanding Coronary Arteriosclerosis. Royal College of Physicians of Edinburgh, Royal College, England, 2000

    Google Scholar 

  96. Heart Disease: ATextbook of Cardiovascular Medicine. W.B. Saunders Company, 2001, pp 2297

  97. Wei M, Gaskill SP, Haffner SM, Stern MP: Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care 21: 1167–1172, 1998

    Google Scholar 

  98. Folsom AR, Eckfeldt JH, Weitzman S, Ma J, Chambless LE, Barnes RW, Cram KB, Hutchinson RG: Relation of carotid artery wall thick-ness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Stroke 25: 66–73, 1994

    Google Scholar 

  99. Temelkova-Kurktschiev TS, Koehler C, Leonhardt W, Schaper F, Henkel E, Siegert G, Hanefeld M: Increased intimal-medial thick-ness in newly detected type 2 diabetes: Risk factors. Diabetes Care 22: 333–338, 1999

    Google Scholar 

  100. Wagenknecht LE, D'Agostino RB, Haffner SM, Savage PJ, Rewers M: Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: The Insulin Resistance Atherosclerosis Study. Diabetes Care 21: 1812–1818, 1998

    Google Scholar 

  101. Hanefeld M, Koehler C, Schaper F, Fuecker K, Henkel E, Temelkova-Kurktschiev T: Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. Atherosclerosis 144: 229–235, 1999

    Google Scholar 

  102. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340: 14–22, 1999

    Google Scholar 

  103. Brownlee M: Glycation products and the pathogenesis of diabetic complications. Diabetes Care 15: 1835–1843, 1992

    Google Scholar 

  104. Vlassara H, Bucala R: Recent progress in advanced glycation and diabetic vascular disease: Role of advanced glycation end product receptors. Diabetes 45(suppl 3): S65–S66, 1996

    Google Scholar 

  105. Nishikawa T, Edelstein D, Brownlee M: The missing link: A single unifying mechanism for diabetic complications. Kidney Int Suppl 77: S26–S30, 2000

    Google Scholar 

  106. Opie L: Angiotensin Converting Enzyme Inhibitors: The Advance Continues. Author's Publishing House, University of Capetown Press, 1999, pp 31–32

  107. Sawyer DB, Colucci WS: Mitochondrial oxidative stress in heart fail-ure: "Oxygen wastage" revisited. Circ Res 86: 119–120, 2000

    Google Scholar 

  108. Singal PK, Khaper N, Farahmand F, Bello-Klein A: Oxidative stress in congestive heart failure. 2: 206–211, 2000

    Google Scholar 

  109. Tirosh A, Potashnik R, Bashan N, Rudich A: Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. J Biol Chem 274: 10595–10602, 1999

    Google Scholar 

  110. Mohanty PA, Aljada A: Rosiglitazone improves vascular reactivity, inhibits reactive oxygen species (ROS) generation, reduces p47phox subunit expression in mononuclear cells (MNC) and reduces C reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1): Evidence of a potent anti-inflammatory effect. 2001, abstract pp 276

  111. Ghanim H, Garg R, Aljada A, Mohanty P, Kumbkarni Y, Assian E, Hamouda W, Dandona P: Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: Evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. J Clin Endocrinol Metab 86: 1306–1312, 2001

    Google Scholar 

  112. Nystrom FH, Quon MJ: Insulin signalling: Metabolic pathways and mechanisms for specificity. Cell Signal 11: 563–574, 1999

    Google Scholar 

  113. Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD: Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 49: 1231–1238, 2000

    Google Scholar 

  114. Feener EP, King GL: Vascular dysfunction in diabetes mellitus. Lancet 350(suppl 1): SI9–SI13, 1997

    Google Scholar 

  115. Koya D, King GL: Protein kinase C activation and the development of diabetic complications. Diabetes 47: 859–866, 1998

    Google Scholar 

  116. Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, Feener EP, Herbert TP, Rhodes CJ, King GL: Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: A specific vascular action of insulin. Circulation 101: 676–681, 2000

    Google Scholar 

  117. Terry CM, Callahan KS: Protein kinase C regulates cytokine-induced tissue factor transcription and procoagulant activity in human endothelial cells. J Lab Clin Med 127: 81–93, 1996

    Google Scholar 

  118. Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, Bursell SE, Kern TS, Ballas LM, Heath WF, Stramm LE, Feener EP, King GL: Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 272: 728–731, 1996

    Google Scholar 

  119. Giles TD, Ouyang J, Kerut EK, Given MB, Allen GE, McIlwain EF, Greenberg SS: Changes in protein kinase C in early cardiomyopathy and in gracilis muscle in the BB/W or diabetic rat. Am J Physiol 274: H295–H307, 1998

    Google Scholar 

  120. Gowri MS, Van der Westhuyzen DR, Bridges SR, Anderson JW: Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may be due to the abnormal com-position of HDL. Arterioscler Thromb Vasc Biol 19: 2226–2233, 1999

    Google Scholar 

  121. Huang ES, Meigs JB, Singer DE: The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. Am J Med 111: 633–642, 2001

    Google Scholar 

  122. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285: 2486–2497, 2001

    Google Scholar 

  123. Bergman RN: Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38: 1512–1527, 1989

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. General Hospital, San Fernando, Trinidad

    Steve Ian Smith

Authors
  1. Steve Ian Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, S.I. PPAR-γ receptor agonists—a review of their role in diabetic management in Trinidad and Tobago. Mol Cell Biochem 263, 189–210 (2004). https://doi.org/10.1023/B:MCBI.0000041861.79585.4b

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000041861.79585.4b

Search

Navigation