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Pancreatic β-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt?

Pancreatic β-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase... The control of pancreatic -cell growth and survival in the adult plays a pivotal role in the pathogenesis of type 2 diabetes. In certain insulin-resistant states, such as obesity, the increased insulin-secretory demand can often be compensated for by an increase in -cell mass, so that the onset of type 2 diabetes is avoided. This is why approximately two-thirds of obese individuals do not progress to type 2 diabetes. However, the remaining one-third of obese subjects that do acquire type 2 diabetes do so because they have inadequate compensatory -cell mass and function. As such, type 2 diabetes is a disease of insulin insufficiency. Indeed, it is now realized that, in the vast majority of type 2 diabetes cases, there is a decreased -cell mass caused by a marked increase in -cell apoptosis that outweighs rates of -cell mitogenesis and neogenesis. Thus a means of promoting -cell survival has potential therapeutic implications for treating type 2 diabetes. However, understanding the control of -cell growth and survival at the molecular level is a relatively new subject area of research and still in its infancy. Notwithstanding, recent advances have implicated signal transduction via insulin receptor substrate-2 (IRS-2) and downstream via protein kinase B (PKB, also known as Akt) as critical to the control of -cell survival. In this review, we highlight the mechanism of IRS-2, PKB, and anti-apoptotic PKB substrate control of -cell growth and survival, and we discuss whether these may be targeted therapeutically to delay the onset of type 2 diabetes. apoptosis; obesity; insulin receptor substrate-2; protein kinase B substrates Address for reprint requests and other correspondence: C. J. Rhodes, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122 (E-mail: cjr@pnri.org ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

Pancreatic β-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt?

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1849
eISSN
1522-1555
DOI
10.1152/ajpendo.00031.2004
pmid
15271644
Publisher site
See Article on Publisher Site

Abstract

The control of pancreatic -cell growth and survival in the adult plays a pivotal role in the pathogenesis of type 2 diabetes. In certain insulin-resistant states, such as obesity, the increased insulin-secretory demand can often be compensated for by an increase in -cell mass, so that the onset of type 2 diabetes is avoided. This is why approximately two-thirds of obese individuals do not progress to type 2 diabetes. However, the remaining one-third of obese subjects that do acquire type 2 diabetes do so because they have inadequate compensatory -cell mass and function. As such, type 2 diabetes is a disease of insulin insufficiency. Indeed, it is now realized that, in the vast majority of type 2 diabetes cases, there is a decreased -cell mass caused by a marked increase in -cell apoptosis that outweighs rates of -cell mitogenesis and neogenesis. Thus a means of promoting -cell survival has potential therapeutic implications for treating type 2 diabetes. However, understanding the control of -cell growth and survival at the molecular level is a relatively new subject area of research and still in its infancy. Notwithstanding, recent advances have implicated signal transduction via insulin receptor substrate-2 (IRS-2) and downstream via protein kinase B (PKB, also known as Akt) as critical to the control of -cell survival. In this review, we highlight the mechanism of IRS-2, PKB, and anti-apoptotic PKB substrate control of -cell growth and survival, and we discuss whether these may be targeted therapeutically to delay the onset of type 2 diabetes. apoptosis; obesity; insulin receptor substrate-2; protein kinase B substrates Address for reprint requests and other correspondence: C. J. Rhodes, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122 (E-mail: cjr@pnri.org ).

Journal

AJP - Endocrinology and Metabolism – The American Physiological Society

Published: Aug 1, 2004

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