Abstract
The capacity of β cells to expand in response to insulin resistance is a critical factor in the development of type 2 diabetes. Proliferation of β cells is a major component for these adaptive responses in animal models. The extracellular signals responsible for β-cell expansion include growth factors, such as insulin, and nutrients, such as glucose and amino acids. AKT activation is one of the important components linking growth signals to the regulation of β-cell expansion. Downstream of AKT, tuberous sclerosis complex 1 and 2 (TSC1/2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling have emerged as prime candidates in this process, because they integrate signals from growth factors and nutrients. Recent studies demonstrate the importance of mTORC1 signaling in β cells. This review will discuss recent advances in the understanding of how this pathway regulates β-cell mass and present data on the role of TSC1 in modulation of β-cell mass. Herein, we also demonstrate that deletion of Tsc1 in pancreatic β cells results in improved glucose tolerance, hyperinsulinemia and expansion of β-cell mass that persists with aging.
Original language | English (US) |
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Pages (from-to) | 1892-1902 |
Number of pages | 11 |
Journal | Cell Cycle |
Volume | 11 |
Issue number | 10 |
DOIs | |
State | Published - May 15 2012 |
Bibliographical note
Funding Information:This work was supported by National Institutes of Health Grant DK-073716- (to E.B.M.), Research Grant from The Juvenile Diabetes Research Foundation and a Career Development Award from
Funding Information:
the American Diabetes Association (to E.B.M.). E.U.A. was supported by an NIH training grant (2T32DK071212- 06). We would also acknowledge the MDRTC Cell and Molecular Biology Core (P60DK020572) and the Morphology Core at the University of Michigan Cancer Center for their ser vices. We want to thank the innumerable authors who have contributed to the field of mTOR signaling and β cell signaling and apologize for not being able to cite all of their important contributions because of editorial limitations on the numbers of references allowed.
Keywords
- AKT
- Cell cycle
- Glucose homeostasis
- Insulin
- Islets and proliferation
- S6K
- TSC1
- TSC2
- mTORC1
- β cells
- β-cell signaling