Page 80 - 76_03

ALBERTO BARTOLOMÉ Y COLS. AN. R. ACAD. NAC. FARM.

ER-stress may be involved in ß cell death or survival. At this stage, the
relative expression of IRA versus IRB within the ß cells may play an
essential role in the regulation of pancreatic ß cell proliferation. A bet-
ter knowledge of the molecular mechanisms involved in ß cell plastic-
ity is needed to understand its role in type 2 diabetes progression.

5. ACKNOWLEDGEMENTS

We thank Silvia Fernández and Gema García for their technical assis-
tance. This work was supported by Spanish Ministry of Science and
Innovation Grants SAF2005/00014, SAF2007/60058, and SAF2008/00031.
A. B. acknowledges an FPU grant from the Spanish Ministry of Education.

6. REFERENCES

1. Sorenson, R. L. & Brelje, T. C. (1997) Adaptation of islets of Langerhans to preg-
nancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic
hormones. Horm. Metab. Res. 29(6): 301-307.

2. Pick, A., Clark, J., Kubstrup, C., Levisetti, M., Pugh, W., Bonner-Weir, S. &
Polonsky, K. S. (1998) Role of apoptosis in failure of beta-cell mass compensa-
tion for insulin resistance and beta-cell defects in the male Zucker diabetic fat-
ty rat. Diabetes. 47(3): 358-364.

3. Muoio, D. M. & Newgard, C. B. (2008) Mechanisms of disease: molecular and
metabolic mechanisms of insulin resistance and beta-cell failure in type 2 dia-
betes. Nat. Rev. Mol. Cell Biol. 9(3): 193-205.

4. Withers, D. J., Gutierrez, J. S., Towery, H., Burks, D. J., Ren, J. M., Previs, S.,
Zhang, Y., Bernal, D., Pons, S., Shulman, G. I., Bonner-Weir, S. & White, M. F.
(1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 391(6670):
900-904.

5. Bernal-Mizrachi, E., Wen, W., Stahlhut, S., Welling, C. M. & Permutt, M. A.
(2001) Islet beta cell expression of constitutively active Akt1/PKB alpha induces
striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 108(11):
1631-1638.

6. Pende, M., Kozma, S. C., Jaquet, M., Oorschot, V., Burcelin, R., Le Marchand-
Brustel, Y., Klumperman, J., Thorens, B. & Thomas, G. (2000) Hypoinsulinaemia,
glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature.
408(6815): 994-997.

7. Terauchi, Y., Takamoto, I., Kubota, N., Matsui, J., Suzuki, R., Komeda, K., Hara,
A., Toyoda, Y., Miwa, I., Aizawa, S., Tsutsumi, S., Tsubamoto, Y., Hashimoto,
S., Eto, K., Nakamura, A., Noda, M., Tobe, K., Aburatani, H., Nagai, R. &

374