Skip to main content
Log in

Angiotensin and insulin resistance: Conspiracy theory

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Resistance to the metabolic effects of insulin is a contender for the short list of major cardiovascular risk factors. Since the elements of the syndrome of insulin resistance were first articulated together in 1988, numerous epidemiologic investigations and treatment endeavors have established a relationship between the metabolic disarray of impaired insulin action and cardiovascular disease. Angiotensin II, the primary effector of the renin-angiotensin system, has also achieved a place in the chronicles of cardiovascular risk factors. Conspiracy mechanisms by which angiotensin II and insulin resistance interact in the pathogenesis of cardiovascular disease are reviewed, with particular attention to recent developments in this engaging area of human research.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Reaven GM: Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988, 37:1595–1607.

    Article  PubMed  CAS  Google Scholar 

  2. Peters N, Hales CN: Plasma-insulin concentrations after myocardial infarction. Lancet 1965, I:1144–1145.

    Article  Google Scholar 

  3. Ferrannini E, Buzzigoli G, Bonadonna R, et al.: Insulin resistance in essential hypertension. N Engl J Med 1987, 317:350–357.

    Article  PubMed  CAS  Google Scholar 

  4. Townsend RR, DiPette DJ, Lieux TR, Wolfe RR: The role of the renin-angiotensin system in insulin sensitivity in normotensive subjects. Am J Med Sci 1993, 305:67–71.

    Article  PubMed  CAS  Google Scholar 

  5. Townsend RR, Zhao H: Plasma renin activity and insulin sensitivity in normotensive subjects. Am J Hypertens 1994, 7:894–898.

    PubMed  CAS  Google Scholar 

  6. Ferrannini E, Seghieri G, Muscelli E: Insulin and the reninangiotensin-aldosterone system: influence of ACE inhibition. J Cardiovasc Pharmacol 1994, 24(Suppl 3):S61-S69.

    PubMed  CAS  Google Scholar 

  7. Buchanan TA, Thawani H, Kades W, et al.: Angiotensin II increases glucose utilization during acute hyperinsulinemia via a hemodynamic mechanism. J Clin Invest 1993, 92:720–726.

    PubMed  CAS  Google Scholar 

  8. Townsend RR, DiPette DJ: Pressor doses of angiotensin-II increase insulin-mediated glucose uptake in normotensive man. Am J Physiol 1993, 265:E362-E366.

    PubMed  CAS  Google Scholar 

  9. Brod J, Hejl Z, Hornych A, et al.: Comparison of haemodynamic effects of equipressor doses of intravenous angiotensin and noradrenaline in man. Clin Sci 1969, 36:161–172.

    PubMed  CAS  Google Scholar 

  10. DeFronzo RA: Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. J Cardiovasc Pharmacol 1992, 20(Suppl 11):S1-S16.

    PubMed  Google Scholar 

  11. Nickenig G, Roling J, Strehlow K, et al.: Insulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms. Circulation 1998, 98:2453–2460. This investigation provides direct support for an interaction between insulin and Ang II, in that insulin impairs the post-transcriptional degradation of the AT1 receptors resulting in an increase in their number in the cell membrane, with full preservation of their ability to respond to Ang II.

    PubMed  CAS  Google Scholar 

  12. Folli F, Kahn CR, Hansen H, et al.: Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/ angiotensin II crosstalk. J Clin Invest 1997, 100:2158–2169.

    Article  PubMed  CAS  Google Scholar 

  13. Bernobich E, de Angelis L, Lerin C, Bellini G: The role of the angiotensin system in cardiac glucose homeostasis: therapeutic implications. Drugs 2002, 62:1295–1314.

    Article  PubMed  CAS  Google Scholar 

  14. Kohler H-P: Insulin resistance syndrome: interaction with coagulation and fibrinolysis. Swiss Med Wkly 2002, 132:241–252. Really nice review of the insulin resistance syndrome.

    PubMed  Google Scholar 

  15. Hamsten A, Wiman B, de Faire U, Blomback M: Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985, 313:1557–1563.

    Article  PubMed  CAS  Google Scholar 

  16. Srikumar N, Brown NJ, Hopkins PN, et al.: PAI-1 in human hypertension: relation to hypertensive groups. Am J Hypertens 2002, 15:683–690.

    Article  PubMed  CAS  Google Scholar 

  17. van Oostrom AJ, Cabezas MC, Rabelink TJ: Insulin resistance and vessel endothelial function. J R Soc Med 2002, 95(Suppl 42):54–61.

    PubMed  Google Scholar 

  18. Miatello R, Risler N, Gonzalez S, et al.: Effects of enalapril on the vascular wall in an experimental model of syndrome X. Am J Hypertens 2002, 15:872.

    Article  PubMed  CAS  Google Scholar 

  19. Evans JL, Goldfine ID, Maddux BA, Grodsky GM: Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrinol Rev 2002, 23:599–622.

    Article  CAS  Google Scholar 

  20. Landmesser U, Cai H, Dikalov S, et al.: Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 2002, 40:511–515.

    Article  PubMed  CAS  Google Scholar 

  21. Miyata T, Van Ypersele DS, Ueda Y, et al.: Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol 2002, 13:2478–2487. Interesting study showing similar effects of ACE inhibitors and ARBs in human volunteers on parameters of glucose metabolism.

    Article  PubMed  CAS  Google Scholar 

  22. Yusuf S, Sleight P, Pogue J, et al.: Effects of an angiotensinconverting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. Clin Nephrol 2000, 342:145–153.

    CAS  Google Scholar 

  23. Hansson L, Lindholm LH, Niskanen L, et al.: Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999, 353:611–616.

    Article  PubMed  CAS  Google Scholar 

  24. Dahlof B, Devereux RB, Kjeldsen SE, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002, 359:995–1003.

    Article  PubMed  CAS  Google Scholar 

  25. Lind L, Andersson PE, Andren B, et al.: Left ventricular hypertrophy in hypertension is associated with the insulin resistance metabolic syndrome. J Hypertens 1995, 13:433–438.

    PubMed  CAS  Google Scholar 

  26. Gress TW, Nieto FJ, Shahar E, et al.: Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. Clin Nephrol 2000, 342:905–912.

    CAS  Google Scholar 

  27. Corry DB, Tuck ML: Glucose and insulin metabolism in hypertension. Am J Nephrol 1996, 16:223–236.

    Article  PubMed  CAS  Google Scholar 

  28. Goldstein BJ: Protein-tyrosine phosphatases: emerging targets for therapeutic intervention in type 2 diabetes and related states of insulin resistance. J Clin Endocrinol Metab 2002, 87:2474–2480. Intriguing look at possible avenue for therapy of insulin resistance and type 2 diabetes in the future.

    Article  PubMed  CAS  Google Scholar 

  29. Diep QN, El Mabrouk M, Cohn JS, et al.: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferatoractivated receptor-gamma. Circulation 2002, 105:2296–2302.

    Article  PubMed  CAS  Google Scholar 

  30. Moan A, Risanger T, Eide I, Kjeldsen SE: The effect of angiotensin II receptor blockade on insulin sensitivity and sympathetic nervous system activity in primary hypertension. Blood Press 1994, 3:185–188.

    PubMed  CAS  Google Scholar 

  31. Moan A, Hoieggen A, Seljeflot I, et al.: The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity. J Hypertens 1996, 14:1093–1097.

    Article  PubMed  CAS  Google Scholar 

  32. Laakso M, Karjalainen L, Lempiainen-Kuosa P: Effects of losartan on insulin sensitivity in hypertensive subjects. Hypertension 1996, 28:392–396.

    PubMed  CAS  Google Scholar 

  33. Paolisso G, Tagliamonte MR, Gambardella A, et al.: Losartan mediated improvement in insulin action is mainly due to an increase in non-oxidative glucose metabolism and blood flow in insulin-resistant hypertensive patients. J Hum Hypertens 1997, 11:307–312.

    Article  PubMed  CAS  Google Scholar 

  34. Fogari R, Zoppi A, Preti P, et al.: Differential effects of ACEinhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women. Am J Hypertens 2001, 14(9 Pt 1):921–926.

    Article  PubMed  CAS  Google Scholar 

  35. Nielsen S, Hove KY, Dollerup J, et al.: Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes. Diabetes Obes Metab 2001, 3:463–471.

    Article  PubMed  CAS  Google Scholar 

  36. Fishman S, Rapoport MJ, Weissgarten J, et al.: The effect of Losartan on insulin resistance and beta cell function in chronic hemodialysis patients. Ren Fail 2001, 23:685–692.

    Article  PubMed  CAS  Google Scholar 

  37. Hanefeld M, Abletshauser C: Effect of the angiotensin II receptor antagonist valsartan on lipid profile and glucose metabolism in patients with hypertension. J Int Med Res 2001, 29:270–279.

    PubMed  CAS  Google Scholar 

  38. Luzio SD, Dunseath G, Owens DR: Acute effects of valsartan on insulin sensitivity in obese, non-hypertensive subjects with and without type 2 diabetes. Horm Metab Res 2002, 34:271–274.

    Article  PubMed  CAS  Google Scholar 

  39. Iimura O, Shimamoto K, Matsuda K, et al.: Effects of angiotensin receptor antagonist and angiotensin converting enzyme inhibitor on insulin sensitivity in fructose-fed hypertensive rats and essential hypertensives. Am J Hypertens 1995, 8(4 Pt 1):353–357.

    Article  PubMed  CAS  Google Scholar 

  40. Higashiura K, Ura N, Miyazaki Y, Shimamoto K: Effect of an angiotensin II receptor antagonist, candesartan, on insulin resistance and pressor mechanisms in essential hypertension. J Hum Hypertens 1999, 13(Suppl 1):S71-S74.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Townsend, R.R. Angiotensin and insulin resistance: Conspiracy theory. Current Science Inc 5, 110–116 (2003). https://doi.org/10.1007/s11906-003-0066-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-003-0066-1

Keywords

Navigation