Control of pancreatic β-cell fate by insulin signaling: The sweet spot hypothesis

James D. Johnson, Emilyn U. Alejandro

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

Diabetes results from an absolute or relative deficiency in functional pancreatic β-cell mass. Over the past few years, there has been renewed interest in the role of insulin itself in the regulation of β-cell fate. Numerous animal models point to a critical role for β-cell insulin signaling in the survival and proliferation of pancreatic β-cells. In the present article, we review new studies that elucidate the mechanism by which insulin exerts anti-apoptotic and promitogenic effects on β-cells. In particular, we highlight the emerging role for Raf-1 kinase in autocrine insulin signaling and β-cell fate decisions. We also discuss provocative evidence that the relationship between the dose of insulin and the birth and death of β-cells is not linear. We propose a new hypothesis based on these findings, called the 'sweet spot' hypothesis, that can explain how both upward and downward deviations from normal levels of autocrine/paracrine insulin signaling might play an important role in the pathogenesis of type 1 diabetes and type 2 diabetes. We also highlight the key experiments that are required to further test this hypothesis.

Original languageEnglish (US)
Pages (from-to)1343-1347
Number of pages5
JournalCell Cycle
Volume7
Issue number10
DOIs
StatePublished - May 15 2008

Keywords

  • Autocrine insulin signaling
  • Pancreatic islets
  • Raf-1 kinase

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