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Comment
. 2007 May 22;104(21):8681-2.
doi: 10.1073/pnas.0702844104. Epub 2007 May 16.

When the usual insulin is just not enough

Catherine E Gleason  1 , Danielle N Gross, Morris J Birnbaum
Affiliations
Comment

When the usual insulin is just not enough

Catherine E Gleason et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Insulin resistance provokes expansion of the adult beta cell mass, probably by stimulating proliferation of mature beta cells. In their report, Okada et al. (4) show that such compensatory hyperplasia requires the presence of insulin receptors but not insulin-like growth factor 1 (IGF-1) receptors. They describe two models to explain this process. In the first (Left), insulin resistance leads to an increase in circulating glucose, which, through the carbohydrate sensor glucokinase (Gck), augments insulin secretion from the beta cell. The insulin then acts in an autocrine/paracrine manner to activate a well described signaling cascade through IRS2 and Akt to initiate cell growth. This process is independent of the IGF-1 receptor. In an alternative mechanism (Right), insulin resistance also leads to an increase in glucose as well as other unknown factors that act on the beta cell. The critical difference in this model, however, is that insulin is not the primary initiating signal for growth but provides a permissive input to allow response to glucose or other factors by another mechanism, possibly also dependent on Gck. Note that in both cases, the hyperplastic response is absolutely dependent on cellular insulin but not IGF-1 receptors, as clearly shown by Okada et al.
See this image and copyright information in PMC

Comment on

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