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
. 2006 Jul;116(7):1756-60.
doi: 10.1172/JCI29189.

Insulin resistance and pancreatic beta cell failure

Masato Kasuga  1
Affiliations
Review

Insulin resistance and pancreatic beta cell failure

Masato Kasuga. J Clin Invest. 2006 Jul.

Abstract

It is now well accepted that diabetes mellitus is one of the main threats to human health in the twenty-first century. The total number of people with diabetes worldwide was estimated at between 151 million and 171 million in 2000 and is projected to increase to 221 million in 2010 and to 366 million in 2030. Needless to say, the increase in the number of people with diabetes will be accompanied by an increase in the number of those with diabetic complications such as nephropathy, retinopathy, neuropathy, and atherosclerosis. The global mortality attributable to diabetes in the year 2000 was estimated at 2.9 million deaths, a number that will also increase. Given that type 2 diabetes accounts for more than 90% of cases of diabetes worldwide, it is important that we understand the pathogenesis of this condition and develop new approaches to its prevention and treatment.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Development of type 2 diabetes.
Insulin resistance associated with obesity is induced by adipokines, FFAs, and chronic inflammation in adipose tissue. Pancreatic β cells compensate for insulin resistance by hypersecretion of insulin. However, at some point, β cell compensation is followed by β cell failure, and diabetes ensues.
Figure 2
Figure 2. Insulin signaling in cells.
Insulin elicits its effects by binding to its specific receptor and activating its tyrosine kinase. The activated insulin receptor kinase phosphorylates the intracellular substrate IRS, which then binds various signaling molecules containing the SH2 domain. Among them, the Grb2-Sos complex and SHP-2 transmit mitogenic signals through the activation of Ras. In contrast, PI3K (class IA) transmits the major metabolic actions of insulin via downstream effectors such as phosphoinositide-dependent kinase 1 (PDK1) and Akt.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anderson J.W., Kendall C.W., Jenkins D.J. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. . J. Am. Coll. Nutr. 2003;22:331–339. - PubMed
    1. Shepherd P.R., Withers D.J., Siddle K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signaling. Biochem. J. 1998;333:471–490. - PMC - PubMed
    1. Michael M.D., et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell. 2000;6:87–94. - PubMed
    1. Miyake K., et al. Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. J. Clin. Invest. 2002;110:1483–1491. doi: 10.1172/JCI200215880. - DOI - PMC - PubMed
    1. Bruning J.C., et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell. 1998;2:559–569. - PubMed

MeSH terms