The cardiovascular effects of insulin

Expert Opinion on Drug Safety

Volumn 13, Issue 7, 2014, Pages 955-966

  Younk, Lisa M ^a   Lamos, Elizabeth M ^a   Davis, Stephen N ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiovascular disease; Diabetes mellitus; Endothelium; Insulin; Insulin resistance

Indexed keywords

ADIPONECTIN; ANGIOTENSIN; ANGIOTENSIN[1-7]; CYCLIC GMP; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENDOTHELIN 1; GHRELIN; GLUCAGON LIKE PEPTIDE 1; GLUCOSE TRANSPORTER 4; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; GUANYLATE CYCLASE; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; INSULIN RECEPTOR SUBSTRATE 2; LEPTIN; MYOSIN LIGHT CHAIN PHOSPHATASE; NITRIC OXIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; REACTIVE OXYGEN METABOLITE; RESISTIN; VASCULAR CELL ADHESION MOLECULE 1;

ADRENERGIC SYSTEM; BLOOD PRESSURE REGULATION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR RISK; DIABETES MELLITUS; DRUG MECHANISM; ENDOTHELIAL PROGENITOR CELL; ENDOTHELIUM; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN INFUSION; INSULIN SENSITIVITY; INSULIN TREATMENT; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PANCREAS ISLET CELL FUNCTION; REVIEW; SMOKING CESSATION; SODIUM ABSORPTION; TREATMENT OUTCOME; VASOCONSTRICTION; VASODILATATION; CARDIOVASCULAR SYSTEM; CHEMICALLY INDUCED; DRUG EFFECTS; RISK FACTOR;

CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; ENDOTHELIUM; HUMANS; INSULIN; RISK FACTORS;

EID: 84902662418     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2014.919256     Document Type: Review

References (88)

1. World Health Organization. The top 10 causes of death. 2013. Available from: http://www.who. int/mediacentre/factsheets/fs310/en/[Last accessed 24 February 2014]
2. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173-94
3. Zimmet PZ. Hyperinsulinemia-how innocent a bystander? Diabetes Care 1993;16(Suppl 3):56-70
4. Aroor AR, McKarns S, Demarco VG, et al. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance. Metabolism 2013;62:1543-52
5. Stout RW. Insulin and atheroma. 20-yr perspective. Diabetes Care 1990;13:631-54
6. Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979;2:131-41
7. Fontbonne AM, Eschwege EM. Insulin and cardiovascular disease. Paris prospective study. Diabetes Care 1991;14:461-9
8. Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 1979;2:154-60
9. Eschwege E, Richard JL, Thibult N, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris prospective study, ten years later. Horm Metab Res Suppl 1985;15:41-6
10. Shanik MH, Xu Y, Skrha J, et al. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care 2008;31(Suppl 2):S262-8
11. Yu Q, Gao F, Ma XL. Insulin says NO to cardiovascular disease. Cardiovasc Res 2011;89:516-24
12. Muniyappa R, Montagnani M, Koh KK, Quon MJ. Cardiovascular actions of insulin. Endocr Rev 2007;28:463-91
13. Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am 2008;37:685-711; ix-x
14. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992;15:318-68
15. Mather KJ. The vascular endothelium in diabetes-a therapeutic target? Rev Endocr Metab Disord 2013;14:87-99
16. Steinberg HO, Brechtel G, Johnson A, et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172-9
17. Scherrer U, Randin D, Vollenweider P, et al. Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Invest 1994;94:2511-15
18. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-7
19. Zeng G, Nystrom FH, Ravichandran LV, et al. Roles for insulin receptor, PI3-kinase, and akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 2000;101:1539-45
20. Dimmeler S, Fleming I, Fisslthaler B, et al. Activation of nitric oxide synthase in endothelial cells by akt-dependent phosphorylation. Nature 1999;399:601-5
21. Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 2003;284:R1-12
22. Lincoln TM, Dey N, Sellak H. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol (1985) 2001;91:1421-30
23. Begum N, Ragolia L, Rienzie J, et al. Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells. evaluation of the role of the nitric oxide signaling pathway and potential defects in hypertension. J Biol Chem 1998;273:25164-70
24. Vincent MA, Barrett EJ, Lindner JR, et al. Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. Am J Physiol Endocrinol Metab 2003;285:E123-9
25. Zhang L, Vincent MA, Richards SM, et al. Insulin sensitivity of muscle capillary recruitment in vivo. Diabetes 2004;53:447-53
26. Vincent MA, Clerk LH, Lindner JR, et al. Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab 2006;290:E1191-7
27. Vincent MA, Clerk LH, Lindner JR, et al. Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes 2004;53:1418-23
28. Barrett EJ, Eggleston EM, Inyard AC, et al. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia 2009;52:752-64
29. Barrett EJ, Wang H, Upchurch CT, Liu Z. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab 2011;301:E252-63
30. Sherwin RS, Kramer KJ, Tobin JD, et al. A model of the kinetics of insulin in man. J Clin Invest 1974;53:1481-92
31. Chiu JD, Richey JM, Harrison LN, et al. Direct administration of insulin into skeletal muscle reveals that the transport of insulin across the capillary endothelium limits the time course of insulin to activate glucose disposal. Diabetes 2008;57:828-35
32. Aird WC. Phenotypic heterogeneity of the endothelium: I. structure, function, and mechanisms. Circ Res 2007;100:158-73
33. Eggleston EM, Jahn LA, Barrett EJ. Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake. Diabetes 2007;56:2958-63
34. Scherrer U, Sartori C. Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulin sensitivity, and cardiovascular morbidity. Circulation 1997;96:4104-13
35. Kubota T, Kubota N, Kadowaki T. The role of endothelial insulin signaling in the regulation of glucose metabolism. Rev Endocr Metab Disord 2013;14:207-16
36. Potenza MA, Addabbo F, Montagnani M. Vascular actions of insulin with implications for endothelial dysfunction. Am J Physiol Endocrinol Metab 2009;297:E568-77
37. Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab 2009;20:295-302
38. Mukai Y, Wang CY, Rikitake Y, Liao JK. Phosphatidylinositol 3-kinase/protein kinase akt negatively regulates plasminogen activator inhibitor type 1 expression in vascular endothelial cells. Am J Physiol Heart Circ Physiol 2007;292:H1937-42
39. Montagnani M, Golovchenko I, Kim I, et al. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J Biol Chem 2002;277:1794-9
40. Luscher TF, Yang Z, Tschudi M, et al. Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Circ Res 1990;66:1088-94
41. Kelly LK, Wedgwood S, Steinhorn RH, Black SM. Nitric oxide decreases endothelin-1 secretion through the activation of soluble guanylate cyclase. Am J Physiol Lung Cell Mol Physiol 2004;286:L984-91
42. Mather KJ, Mirzamohammadi B, Lteif A, et al. Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes 2002;51:3517-23
43. Mather KJ, Lteif A, Steinberg HO, Baron AD. Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 2004;53:2060-6
44. Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1. Adv Pharmacol 2010;60:1-26
45. Baron AD, Brechtel G. Insulin differentially regulates systemic and skeletal muscle vascular resistance. Am J Physiol 1993;265:E61-7
46. Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI 3-kinase-and MAP kinase-mediated signaling in human muscle. J Clin Invest 2000;105:311-20
47. Potenza MA, Marasciulo FL, Chieppa DM, et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 2005;289:H813-22
48. Piatti PM, Monti LD, Conti M, et al. Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes 1996;45:316-21
49. Nilsson D, Wackenfors A, Gustafsson L, et al. PKC and MAPK signalling pathways regulate vascular endothelin receptor expression. Eur J Pharmacol 2008;580:190-200
50. Li G, Barrett EJ, Wang H, et al. Insulin at physiological concentrations selectively activates insulin but not insulin-like growth factor I (IGF-I) or insulin/IGF-I hybrid receptors in endothelial cells. Endocrinology 2005;146:4690-6
51. Sartori C, Trueb L, Nicod P, Scherrer U. Effects of sympathectomy and nitric oxide synthase inhibition on vascular actions of insulin in humans. Hypertension 1999;34:586-9
52. Marban S, Roth J. Transgenic hyperinsulinemia: a mouse model of insulin resistance and glucose intolerance without obesity. In: Shafrir E, editor. Lessons from animal diabetes VI. 6th edition. Birkhauser, Boston; 1996. p. 201; 202-224
53. Rizza RA, Mandarino LJ, Genest J, et al. Production of insulin resistance by hyperinsulinaemia in man. Diabetologia 1985;28:70-5
54. Gavin JR III, Roth J, Neville DM Jr, et al. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci USA 1974;71:84-8
55. Pederson TM, Kramer DL, Rondinone CM. Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation. Diabetes 2001;50:24-31
56. Dominici FP, Burghi V, Munoz MC, Giani JF. Modulation of the action of insulin by angiotensin-(1-7). Clin Sci (Lond) 2014;126:613-30
57. Sheikh A. Direct cardiovascular effects of glucagon like peptide-1. Diabetol Metab Syndr 2013;5:47
58. Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis 2013;227:216-21
59. Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Insulin as an anti-inflammatory and antiatherogenic modulator. J Am Coll Cardiol 2009;53:S14-20
60. Imrie H, Abbas A, Kearney M. Insulin resistance, lipotoxicity and endothelial dysfunction. Biochim Biophys Acta 2010;1801:320-6
61. Schulz E, Jansen T, Wenzel P, et al. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 2008;10:1115-26
62. Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res 2006;71:247-58
63. Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Anti-inflammatory effects of insulin and the pro-inflammatory effects of glucose. Semin Thorac Cardiovasc Surg 2006;18:293-301
64. Zhou MS, Schulman IH, Zeng Q. Link between the renin-angiotensin system and insulin resistance: implications for cardiovascular disease. Vasc Med 2012;17:330-41
65. Andreozzi F, Laratta E, Sciacqua A, et al. Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells. Circ Res 2004;94:1211-18
66. Park K, Li Q, Rask-Madsen C, et al. Serine phosphorylation sites on IRS2 activated by angiotensin II and protein kinase C to induce selective insulin resistance in endothelial cells. Mol Cell Biol 2013;33:3227-41
67. Pan P, Fu H, Zhang L, et al. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells. BMC Cell Biol 2010;11:36
68. Madonna R, De Caterina R. Cellular and molecular mechanisms of vascular injury in diabetes-part II: cellular mechanisms and therapeutic targets. Vascul Pharmacol 2011;54:75-9
69. Aroor AR, Mandavia CH, Sowers JR. Insulin resistance and heart failure: molecular mechanisms. Heart Fail Clin 2012;8:609-17
70. Meinert CL, Knatterud GL, Prout TE, Klimt CR. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. mortality results. Diabetes 1970;19(Suppl 2):789-830
71. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53
72. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65
73. The Diabetes Control and Complications Trial Research 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 1993;329:977-86
74. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643-53
75. Ceriello A. Hypothesis: the "metabolic memory", the new challenge of diabetes. Diabetes Res Clin Pract 2009;86(Suppl 1):S2-6
76. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39
77. ACCORD Study Group. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85
78. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest 2000;106:453-8
79. ADVANCE Collaborative Group, Patel A. MacMahon S, Chalmers J, Neal B, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-72
80. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-93
81. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-12
82. BARI 2D Study Group. Frye RL, August P, Brooks MM, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503-15
83. Mellbin LG, Malmberg K, Norhammar A, et al. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the diabetes mellitus insulin-glucose infusion in acute myocardial infarction (DIGAMI) 2 study. Diabetologia 2011;54:1308-17
84. Gamble JM, Simpson SH, Eurich DT, et al. Insulin use and increased risk of mortality in type 2 diabetes: a cohort study. Diabetes Obes Metab 2010;12:47-53
85. ORIGIN Trial Investigators. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319-28
86. Control Group. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288-98
87. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010;363:1410-18
88. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010;340:b4909