Mitogenic factors accelerate later-age diseases: Insulin as a paradigm

Mechanisms of Ageing and Development

Volumn 102, Issue 1, 1998, Pages 95-113

  Lev Ran, Arye ^a  

^a Maccabi Sick Fund   (Israel)

Author keywords

Aging; Atherosclerosis; Diabetes; Insulin; Mitogens

Indexed keywords

GROWTH FACTOR; INSULIN; INSULIN RECEPTOR;

AGING; ATHEROSCLEROSIS; CALORIC RESTRICTION; CELL DIVISION; CELL PROLIFERATION; DEMENTIA; DISEASE COURSE; FOOD INTAKE; GENE EXPRESSION; HYPERALIMENTATION; HYPERGLYCEMIA; HYPERINSULINEMIA; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; MITOGENESIS; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; ONSET AGE; PRIORITY JOURNAL; REVIEW; RISK FACTOR;

RODENTIA;

EID: 0032077119     PISSN: 00476374     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0047-6374(98)00027-X     Document Type: Article

References (132)

1. Auwerx J., Bouillon R., Collen D., Geboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis. 8:1988;68-72.
2. Alba, O., Calle, A., Navia, J., 1997. Hyperinsulinemia as a risk factor for coronary artery disease. Diabetologia 40 (Suppl. 1) A448 (abstract 1763).
3. Amatruda, J.M., Welle, S., 1995. Obesity. In: Felig, P., Baxter, J.D., Frohman, L.A. (Eds.) Endocrinology and Metabolism, 3rd ed. McGraw-Hill, New York, pp. 1271-1313.
4. Aviv A., Aviv H. Reflections on telomeres, growth, aging, and essential hypertension. Hypertension. 29:1997;1067-1072.
5. Bergstrom R.W., Newell-Morris L.L., Leonetti D.L., Shuman W.P., Wahl P.W., Fujimoto W.Y. Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in JapaneseAmerican men. Diabetes. 39:1990;104-111.
6. Bierman E.L. Atherogenesis in diabetes. Arterioscler. Thromb. 12:1992;647-659.
7. Bressler P., Bailey S.R., Matsuda M., DeFronzo R.A. Insulin resistance and coronary artery disease. Diabetologia. 39:1996;1345-1350.
8. Bryan T.M., Englezou A., Dalla-Poza L., Dunham M.A., Reddel R.R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 3:1997;1271-1274.
9. Bucht G., Adolfson R., Lithner F., Winblad B. Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. Acta Med. Scand. 213:1983;387-392.
10. Båvenholm P., Proudler A., Silveira A., Crook D., Blomback M., de Faire U., Hamsten A. Relationships of insulin and intact and split proinsulin to haemostatic function in young men with and without coronary artery disease. Thromb. Haemost. 73:1995;568-575.
11. Cagnacci A., Soldani R., Carriero P.L., Paoletti A.M., Fioretti P., Melis G.B. Effects of low doses of transdermal 17-β estradiol on carbohydrate metabolism in postmenopausal women. J. Clin. Endocrinol. Metab. 74:1992;1396-1400.
12. Campisi J. The biology of replicative senescence. Eur. J. Cancer. 33:1997;703-709.
13. Carmelli D., Cardon L.R., Fabsitz R. Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environment? Am. J. Hum. Genet. 55:1994;566-573.
14. Chang E., Harley C.B. Telomere length and replicative aging in human vascular tissues. Proc. Natl Acad. Sci. USA. 92:1995;11190-11194.
15. Charles M.A., Fontbonne A., Thibult N., Warnet J.-M., Rosselin G.E., Eschwege E. Risk factors for NIDDM in White population. Paris Prospective Study. Diabetes. 40:1991;796-799.
16. Collins V.R., Dowse G.K., Zimmet P.Z.et al. Serum insulin and ECG abnormalities suggesting coronary heart disease in the populations of Mauritius and Nauru: cross-sectional and longitudinal associations. J. Clin. Epidemiol. 46:1993;1373-1393.
17. Colwell J.A. The feasibility of intensive insulin management in non-insulin-dependent diabetes mellitus. Ann. Intern. Med. 124:1996;131-135.
18. Comi P., Chiaramonte R., Maier J.A.M. Senescence-dependent regulation of type I plasminogen activator inhibitor in human vascular endothelial cells. Exp. Cell Res. 219:1995;304-308.
19. Craft S., Newcomer S., Kanne S.et al. Memory improvement following induced hyperinsulinemia in Alzheimer's Disease. Neurobiol. Aging. 17:1996;123-130.
20. De Meyts P., Christoffersen C.T., Urs B.et al. Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-1 receptor tyrosine kineses. Metabolism. 44(Suppl. 4):1995;2-11.
21. DeFronzo R.A. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 5:1997;177-269.
22. DeFronzo R.A., Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 14:1991;173-194.
23. Després J.-P., Lamarche B., Maurioge P.et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. New Engl. J. Med. 334:1996;952-957.
24. Dimri G.P., Lee X., Basile G.et al. A biomarker 22 that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA. 92:1995;9363-9367.
25. Engelman R.W., Day N.R., Good R.A. Calories, cell proliferation, and proviral expression in autoimmunity and cancer. Proc. Soc. Exp. Biol. Med. 203:1993;13-17.
26. Feener E.P., King G.L. Vascular dysfunction in diabetes mellitus. Lancet. 350:1997;S19-S113.
27. Ferrannini E., Haffner S.M., Mitchell B.D., Stern M.P. Hyperinsulinemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia. 34:1991;416-422.
28. Ferrara A., Barrett-Connor E., Wingard D.L., Edelstein S.L. Sex differences in insulin levels in older adults and the effect of body size, estrogen replacement therapy and glucose tolerance status: the Rancho Bernardo Study, 1984-1987. Diabetes Care. 18:1995;220-225.
29. Finch C.E., Cohen D.M. Aging, metabolism, and Alzheimer disease: review and hypotheses. Exp. Neurol. 143:1997;82-102.
30. Finch, C.E., 1990. Longevity, Senescence, and the Genome. Chicago. The University of Chicago Press, Chicago.
31. Fontbonne A., Charles M.A., Thibult N.et al. Hyperinsulinemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. Diabetologia. 34:1991;356-361.
32. Fujimoto W.Y., Akanuma Y., Kanazawa Y., Mashiko S., Leonetti D., Wahl P. Plasma insulin levels in Japanese and Japanese-American men with type 2 diabetes may be related to the occurrence of cardiovascular disease. Diabetes Res. Clin. Pract. 6:1989;121-127.
33. Genuth S. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Ann. Intern. Med. 124:1996;104-109.
34. Giddings S.J., Carnaghi L.R. Insulin receptor gene expression during development: developmental regulation of insulin receptor mRNA abundance in embryonic rat liver and yolk sac, developmental regulation of insulin receptor gene splicing, and comparison to abundance of insulin-like growth factor 1 receptor mRNA. Mol. Endocrinol. 6:1992;1665-1672.
35. Goldstein S., Moerman R.E., Soeldner J.S., Gleason R.E., Barnett D.M. Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors. Science. 199:1978;781-782.
36. Goldstein S., Moerman E.J., Fujii S., Sobel B.E. Overexpression of plasminogen activator inhibitor type-l in senescent fibroblasts from normal subjects and those with Werner Syndrome. J. Cell. Physiol. 161:1994;571-579.
37. Haffner S.M., Miettinen H. Insulin resistance implications for type 11 diabetes mellitus and coronary heart disease. Am. J. Med. 103:1997;152-162.
38. Haffner S.M., Stern M.P., Hazuda H.P., Mitchell B.D., Patterson J.K. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? J. Am. Med. Assoc. 263:1990;2893-2898.
39. Hanis C.L., Boerwinkle E., Chakraborty et al R. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat. Genet. 13:1996;161-168.
40. Hansen B.F., Danielsen G.M., Dreier K.et al. Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem. J. 315:1996;271-279.
41. Hargreaves A.D., Logan R.L., Elton R.A., Buchanan K.D., Oliver M.F., Riemersmaa R.A. Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men. Atherosclerosis. 94:1992;61-69.
42. Harley C.B. Telomere loss: mitotic clock or genetic time bomb? Mutat. Res. 256:1991;271-282.
43. Harley C.B., Villeponteau B. Telomeres and telomerase in aging and cancer. Curr. Opin. Genet. Dev. 5:1995;249-255.
44. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37:1965;614-636.
45. Hayflick L. Aging under glass. Mutat. Res. 256:1991;69-80.
46. Hayflick L., Moorhead P.S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:1961;585-621.
47. Henderson S., Allsopp R., Spector D., Wang S.-S., Harley C. In situ analysis of changes in telomere size during replicative aging and cell transformation. J. Cell Biol. 134:1996;1-12.
48. Heydari A.R., Richardson A. Does gene expression play any role in the mechanism of the antiaging effect of dietary restriction? Ann. New York Acad. Sci. 663:1992;384-395.
49. Howard G., O'Leary D.H., Zaccaro D.et al. : Insulin sensitivity and atherosclerosis. Circulation. 93:1996;1809-1817.
50. Humphriss D.B., Stewart M.W., Berrish T.S.et al. Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families. Diabetologia. 40:1997;1185-1190.
51. Ibáñez L., Potau N., Zampolli M., Rique S., Saenger P., Carrascosa A. Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J. Clin. Endocrinol. Metab. 82:1997;2283-2288.
52. Ish-Shalom D., Christoffersen C.T., Vorwerk P.et al. Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetologia. 40(Suppl 2):1997;S25-S31.
53. Janca H.U., Ziegler A.G., Standl E., Mehnert H. Daily insulin dose as a predictor of macrovascular disease in insulin treated non-insulin-dependent diabetics. Diabetes Metab. 13:1987;359-364.
54. Jarrett R.J. Why is insulin not a risk factor for coronary heart disease? Diabetologia. 37:1994;953-955.
55. Jarrett R.J. The cardiovascular risk associated with impaired glucose tolerance. Diabetes Med. 13:1996;S15-S19.
56. Juhan-Vague I., Vague P., Alessi M.C.et al. Relationships between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor. Diabetes Metab. 13:1987;331-336.
57. Jung R.T. Obesity as a disease. Br. Med. Bull. 53:1997;307-321.
58. Kaplan N.M. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch. Int. Med. 149:1989;1514-1520.
59. Katz R.J., Ratner R.E., Cohen R.M., Eisenhower E., Verme D. Are insulin and proinsulin independent risk markers for premature coronary artery disease? Diabetes. 45:1996;736-741.
60. Katzel L.I., Bleecker E.R., Colman E.G., Rogus E.M., Sorkin J.D., Goldberg A.P. Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle-aged and older men. J. Am. Med. Assoc. 274:1995;1918-1921.
61. Kemnitz J.W., Roecker E.B., Weindruch R., Elson D.F., Baum S.T., Bergman R.N. Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys. Am. J. Physiol. 266:1994;E540-E547.
62. Kempermann G., Kuhn H.G., Gage F.H. More hippocampal neurones in adult mice living in an enriched environment. Nature. 386:1997;493-495.
63. King G.L., Kahn C.R. Non-parallel evolution of metabolic and growth-promoting functions of insulin. Nature. 92:1981;644-646.
64. Klimm, H.-D., Jacob, S., 1997. Hyperinsulinemia and dyslipidemia in patients with peripheral vascular disease. Diabetologia 40 (Suppl. 1) A447 (abstract 1759).
65. Kopelman P.G., Albon L. Obesity, non-insulin-dependent diabetes mellitus and the metabolic syndrome. Br. Med. Bull. 53:1997;322-340.
66. Krentz A.J., Nattrass M. Insulin resistance: a multifaceted metabolic syndrome. Insights gained using a low-dose insulin infusion technique. Diabetic Med. 13:1996;30-39.
67. Kuusisto J., Mykkanen L., Helkala E.-L.et al. Association between features of the insulin resistance syndrome and Alzheimer disease independently of apolipoprotein E4 phenotype: cross sectional population based study. Br. Med. J. 315:1997;1045-1049.
68. Laakso M., Sarlund H., Salonen R.et al. Asymptomatic atherosclerosis and insulin resistance. Arterioscler. Thromb. 11:1991;1068-1076.
69. Lane M.A., Ball S.S., Ingram D.K.et al. Diet restriction in rhesus monkeys lowers fasting and glucose-stimulated glucoregulatory end points. Am. J. Physiol. 268:1995;E941-E948.
70. Leibson C.L., Rocca W.A., Hanson V.A.et al. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am. J. Epidemiol. 145:1997;301-308.
71. Leon-Quinto T., Adnot P., Partha B. Alteration of the counterregulatory hormones in the conscious rat after protein-energy restriction. Diabetologia. 40:1997;1028-1034.
72. Linskens M.H.K., Feng J., Andrews W.H.et al. Cataloging altered gene expression in young and senescent cells using enhanced differential display. Nucleic Acid Res. 23:1995;3244-3251.
73. Liu Q.Z., Knowler W.C., Nelson R.G.et al. Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analysis. Diabetes. 41:1992;1141-1150.
74. Lok E., Scott F.W., Mongeau R., Nera E.A., Malcolm S., Clayson D.B. Calorie restriction and cellular proliferation in various tissues in the female Swiss Webster mouse. Cancer Lett. 51:1990;67-73.
75. Manson J.A.E., Colditz G.A., Stampfer M.J.et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch. Intern. Med. 151:1991;1141-1147.
76. Masoro E.J. McCay's hypothesis: undernutrition and longevity. Proc. Nutr Soc. 54:1995;657-664.
77. Masoro E.J., Shimokawa I., Yu B.P. Retardaticn of the aging processes in rats by food restriction. Ann. New York Acad. Sci. 621:1991;337-352.
78. Masoro E.J., McCarter R.J., Katz M.S., McMahan C.A. Dietary restriction alters characteristics of glucose fuel use. J. Gerontol. 47:1992;B202-B208.
79. Meigs J.B., Singer D.E., Sullivan L.M.et al. Metabolic control and prevalent cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM): the NIDDM Patient Outcomes Research Team. Am. J. Med. 102:1997;38-47.
80. Merry B.J., Holehan A.M. In vivo DNA synthesis in the dietary restricted long-lived rat. Exp. Gerontol. 20:1985;15-28.
81. Metcalfe J.A., Parkhill J., Campbell L.et al. Accelerated telomere shortening in ataxia telangiectasia. Nat. Genet. 13:1996;380-383.
82. Modan M., Halkin H., Almog S.et al. Hyperinsulinemia. A link between hypertension, obesity and glucose intolerance. J. Clin. Invest. 75:1985;809-817.
83. Myers M.G., White M.F. Insulin signal transduction and the IRS proteins. Annu. Rev. Pharmacol. Toxicol. 36:1996;615-658.
84. Mykkänen L., Kuusisto J., Pyörälä K., Laakso M. Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia. 36:1993;553-559.
85. Nabulsi A.A., Folsom A.R., Heiss G.et al. Fasting hyperinsulinemia and cardiovascular risk factors in nondiabetic adults: stronger associations in lean versus obese subjects. Metabolism. 44:1995;914-922.
86. Nathan, D.M., Meigs, J., Singer, D.E., 1997. The epidemiology of cardiovascular disease in type 2 diabetes mellitus: how sweet it is. or is it? Lancet 350 si4-si9.
87. Nelson R.G., Sievers M.L., Knowler W.C.et al. Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes. Circulation. 81:1990;987-995.
88. Niskanen L., Uusitupa M., Sarlund H., Siitonen O., Paljarvi I., Laakso M. The effects of weight loss on insulin sensitivity, skeletal muscle composition and capillary density in obese non-diabetic subjects. Int. J. Obes. 20:1996;154-160.
89. O'Shea, J., 1990. Was Mozart Poisoned? Medical investigations into the lives of the great composers. St.Martin's Press, New York.
90. Ogura M., Ogura H., Ikehara S., Dao M.L., Good R.A. Decrease by chronic energy intake restriction of cellular proliferation in the intestinal epithelium and lymphoid organs in autoimmunity-prone mice. Proc. Natl Acad Sci. USA. 86:1989;5918-5922.
91. Orchard T.J., Eichner J., Kuller L.H., Becker D.J., McCallum L.M., Grandits G.A. Insulin as a predictor of coronary heart disease: Interaction with apoE phenotype. A report from MRFIT. Ann. Epidemiol. 4:1994;40-45.
92. Orr W.C. Senescence: in search of causality. Dev. Genet. 18:1996;93-98.
93. Ott, A., Stolk, M.M., Breteler, M.M.b., Hofman, A., 1996. The association between diabetes mellitus and dementia. Neurology 46 A364 (abstract P05.084).
94. Paolisso G., Gambardella A., Ammendola S.et al. Glucose tolerance and insulin action in healthy centenarians. Am. J. Physiol. 270:1996;E890-E894.
95. Peiris A.N., Mueller R.A., Smith G.A. Splanchnic insulin metabolism in obesity: influence of body fat distribution. J. Clin. Invest. 78:1986;1648-1657.
96. Pyörälä K., Savolainen E., Kaukola S., Haapakoski J. Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9.5-year follow-up of the Helsinki Policemen Study population. Acta Med. Scand. 701(Suppl.):1985;38-52.
97. Quiñones Galvan A., Natali A., Muscelli E.et al. Insulin sensitivity in cardiological syndrome X. J. Intern. Med. 239:1996;241-247.
98. Reaven G.M. Role of insulin resistance in human disease. Diabetes. 37:1988;1596-1607.
99. Reaven G.M. Pathophysiology of insulin resistance in human disease. Physiol. Rev. 75:1995;473-486.
100. Reaven G.M., Chen Y.-D. Insulin resistance, its consequences, and coronary heart disease. Must we choose one culprit? Circulation. 93:1996;1780-1783.
101. Reaven G.M., Laws A. Insulin resistance, compensatory hyperinsulinemia, and coronary heart disease. Diabetologia. 37:1994;948-952.
102. Rönnemaa T., Laakso M., Pyörälä K., Kallio V., Puukka P. High fasting plasma insulin as an indicator of coronary heart disease in non-insulin-dependent diabetic patients and nondiabetic subjects. Arterioscler. Thromb. 11:1991;80-90.
103. Rose D.W., Saltiel A.R., Majumdar M., Decker S.J., Olefsky J.M. Insulin receptor substrate 1 is required for insulin-mediated mitogenic signal transduction. Proc. Natl Acad.Sci. USA. 91:1994;797-801.
104. Rowe D.W., Starman B.J., Fujimoro W.Y., Williams R.H. Abnormalities in proliferation and protein synthesis in skin fibroblast cultures from patients with diabetes mellitus. Diabetes. 26:1977;284-290.
105. Rubin H. Cell aging in vivo and in vitro. Mech. Aging Dev. 98:1997;1-35.
106. Saltiel A.R. Diverse signaling pathways in the cellular actions of insulin. Am. J. Physiol. 270:1996;E375-E385.
107. Schneider E.L., Mitsui Y. The relationship between in vitro cellular aging and in vivo human age. Proc. Natl Acad. Sci. USA. 73:1976;3584-3588.
108. Seibrk, M., Vallebo, L., Burchardt, H. et al., 1996. Abnormal glucose tolerance and hyperinsulinemia in patients with coronary artery disease. Diabetologia 39 (Suppl. 1) (abstract 1059).
109. Sheu W.H., Jeng C.Y., Shieh S.M.et al. Insulin resistance and abnormal electrocardiograms in patients with high blood pressure. Am. J. Hypertens. 5:1992;444-448.
110. Shinozaki K., Hara Y., Suzuki M., Harano Y., Ikebuchi M. Demonstration of insulin resistance in coronary artery disease documented with angiography. Diab. Care. 19:1996;1-7.
111. Sicree R.A., Zimmet P.Z., King H.O.M., Coventry J.S. Plasma insulin response among Nauruans. Prediction of deterioration in glucose tolerance over 6 years. Diabetes. 36:1987;179-186.
112. Slagboom P.E., Droog S., Boomsma D.l. Genetic determination of telomere size in humans: a twin study of three age groups. Am. J. Hum. Genet. 55:1994;876-882.
113. Smith J.R., Pereira-Smith O.M. Replicative senescence: implications for in vivo aging and tumor suppression. Science. 273:1996;63-67.
114. Soler A.P., Thompson K.A., Smith R.M., Jarrett L. Immunological demonstration of the accumulation of insulin, but not insulin receptors, in nuclei of insulin-treated cells. Proc. Natl Acad. Sci. USA. 86:1989;6640-6644.
115. Stern M.P. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents? Ann. Intern. Med. 124:1996;110-116.
116. Stout, R.W., 1993. Insulin resistance, hyperinsulinemia, dyslipidemia and atherosclerosis. In: Moller, D.E. (Ed.), Insulin Resistance. Wiley, New York, pp. 355-384.
117. Stout R.W. The impact of insulin upon atherosclerosis. Horm. Metab. Res. 26:1994;125-128.
118. Stout R.W. Hyperinsulinemia and atherosclerosis. Diabetes. 45(Suppl. 3):1996;S45-S46.
119. Taegtmeyer H. Insulin resistance and atherosclerosis. Common roots for two common diseases? Circulation. 93:1996;1777-1779.
120. 3H]thymidine incorporation, cell cycle progression, and cyclin D expression in 3T3-F442A preadipose cells. Endocrinology. 136:1995;3062-3069.
121. Taylor S.I., Accili D., Imai Y. Perspectives in diabetes: Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM? Diabetes. 43:1994;735-740.
122. The DIS Group, Hanefeld M., Schmechel H., Schwanebeck U., Lindner J. Predictors of coronary heart disease and death in NIDDM: the Diabetes Intervention Study experience. Diabetologia. 40(Suppl. 2):1997;S123-S124.
123. Vracko R., Benditt E.P. Restricted replicative life-span of diabetic fibroblasts in vitro: its relation to microangiopathy. Fed. Proc. 34:1975;68-70.
124. Waters S.B., Yamauchi K., Pessin J.E. Functional expression of insulin receptor substrate-1 is required for insulin- stimulated mitogenic signaling. J. Biol. Chem. 238:1993;22231-22234.
125. Weindruch, R., Walford, R.L., 1988. The Retardation of Aging and Disease by Dietary Restriction. Thomas Springfield.
126. Welborn T.W., Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care. 2:1979;154-160.
127. Welin L., Eriksson H., Larsson B., Ohison L.-O., Svårdsudd K., Tibblin G. Hyperinsulinemia is not a major coronary risk factor in elderly men. The study of men born in 1913. Diabetologia. 35:1992;766-770.
128. Willeit J., Kiehl S., Egger G.et al. The role of insulin in age-related differences of cardiovascular risk profile and morbidity. Atherosclerosis. 130:1997;183-189.
129. Wingard D.L., Ferrara A., Barrett-Connor E.L. Is insulin really a heart disease risk factor? Diabetes Care. 18:1995;1299-1304.
130. Wolf N.S., Penn P.E., Jiang D., Riu G.F., Pendergrass W.R. Caloric restriction: conservation of in vivo cellular replicative capacity accompanies life-span extension in mice. Exp. Cell Res. 217:1995;317-323.
131. Zavaroni, I., Bonini, L., Zaccarelli, Z. et al., 1996. Insulin resistance as a risk factor for IGT, NIDDM, hypertension and CHD in a prospective population study. Diabetologia 39 (Suppl. 1) (abstract 251).
132. Zimmet P.Z. Hyperinsulinemia - how innocent a bystander? Diabetes Care. 16(Suppl. 3):1993;56-70.