Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications

Vol. 26, No. 3, 2006

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In-Depth Topic Review

Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications
Pantelis A. Sarafidis^a, Luis M. Ruilope^b

^aHypertension/Clinical Research Center, Department of Preventive Medicine, Rush University Medical Center, Chicago, Ill., USA;
^bHypertension Unit, Hospital 12 de Octubre, Madrid, Spain

Address of Corresponding Author

Am J Nephrol 2006;26:232-244 (DOI: 10.1159/000093632)

Key Words

Insulin resistance
Insulin
Hyperinsulinemia
Kidney
Renal injury

Abstract

Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.

Author Contacts

Pantelis A. Sarafidis, MD, PhD
Hypertension/Clinical Research Center, Department of Preventive Medicine
Rush University Medical Center, 1700 West Van Buren, Suite 470
Chicago, IL 60612 (USA)
Tel. +1 312 563 2831, Fax +1 312 563 2205, E-Mail psarafidis11@yahoo.gr

Article Information

Received: April 24, 2006
Accepted: April 24, 2006
Published online: May 29, 2006
Number of Print Pages : 13
Number of Figures : 2, Number of Tables : 0, Number of References : 149

Medline Abstract (ID 16733348)

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