Horm Metab Res 2010; 42(5): 311-317
DOI: 10.1055/s-0030-1249035
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Exendin-4 Protects Pancreatic Beta Cells from the Cytotoxic Effect of Rapamycin by Inhibiting JNK and p38 Phosphorylation

Y. Kawasaki1 , S. Harashima1 , M. Sasaki1 , E. Mukai1 , 2 , Y. Nakamura1 , N. Harada1 , K. Toyoda1 , A. Hamasaki1 , S. Yamane1 , C. Yamada1 , Y. Yamada1 , 3 , Y. Seino1 , 4 , N. Inagaki1 , 5
  • 1Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 2Japan Association for the Advancement of Medical Equipment, Tokyo, Japan
  • 3Department of Endocrinology and Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita, Japan
  • 4Kansai Electric Power Hospital, Osaka, Japan
  • 5CREST of Japan Science and Technology Cooperation (JST), Kyoto, Japan
Further Information

Publication History

received 19.09.2009

accepted 08.02.2010

Publication Date:
08 March 2010 (online)


It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.



N. Inagaki, MD, PhD 

Department of Diabetes and Clinical Nutrition

Graduate School of Medicine

Kyoto University

54 Shogoin Kawahara-cho


606-8507 Kyoto


Phone: +81/75/751 3560

Fax: +81/75/771 6601

Email: [email protected]