Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jun;20(3):206-10.
doi: 10.1097/MOL.0b013e32832b2024.

Dissecting the role of insulin resistance in the metabolic syndrome

Affiliations
Review

Dissecting the role of insulin resistance in the metabolic syndrome

Joel T Haas et al. Curr Opin Lipidol. 2009 Jun.

Abstract

Purpose of review: Over 20 years ago, insulin resistance was postulated to play a central role in the pathogenesis of the metabolic syndrome. However, this has been difficult to prove, leading to a great deal of controversy within the field. Recent studies on mice and humans with genetic defects in insulin signaling have allowed us, for the first time, to dissect which features of the metabolic syndrome can be caused by insulin resistance.

Recent findings: Liver insulin receptor knockout mice show that hepatic insulin resistance can produce hyperglycemia, increased apolipoprotein B secretion and atherosclerosis, and increased biliary cholesterol secretion and cholesterol gallstones. Many of these changes may be due to disinhibition of the transcription factor, forkhead box O1. Yet, neither liver insulin receptor knockout mice nor humans with insulin receptor mutations develop the hypertriglyceridemia or hepatic steatosis associated with the metabolic syndrome.

Summary: These data point to a central role for insulin resistance in the pathogenesis of the metabolic syndrome, as hyperglycemia, atherosclerosis, and cholesterol gallstones can all be caused by insulin resistance. However, hypertriglyceridemia and hepatic steatosis are not due directly to insulin resistance and should be considered pathogenically distinct features of the metabolic syndrome.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The insulin signaling cascade. Insulin triggers a complex, branching network of signaling events. Shown here is a summary of the major nodes of this cascade, two important transcription factors, Foxo1 and Srebp-1c, and their targets.

References

    1. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA. 2004;291:2847–2850. - PubMed
    1. Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am. 2004;33:283–303. - PubMed
    1. Reaven GM. Banting lecture: Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607. - PubMed
    1. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289–2304. - PubMed
    1. Biddinger SB, Kahn CR. From mice to men: insights into the insulin resistance syndromes. Annu Rev Physiol. 2006;68:123–158. - PubMed

Publication types