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Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide

Abstract

The JNK pathway is known to be activated in several tissues in the diabetic state, and is possibly involved in the development of insulin resistance and suppression of insulin biosynthesis. Here we show a potential new therapy for diabetes using cell-permeable JNK-inhibitory peptide. Intraperitoneal administration of the peptide led to its transduction into various tissues in vivo, and this treatment markedly improved insulin resistance and ameliorated glucose tolerance in diabetic mice. These data indicate that the JNK pathway is critically involved in diabetes and that the cell-permeable JNK-inhibitory peptide may have promise as a new therapeutic agent for diabetes.

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Figure 1: Effects of the JNK- inhibitory peptide, JIP-1-HIV-TAT-FITC, on glucose tolerance in C57BL/KsJ-db/db mice.
Figure 2: Effects of JIP-1-HIV-TAT-FITC on insulin resistance in C57BL/KsJ-db/db mice.
Figure 3: Effects of JIP-1-HIV-TAT-FITC on insulin signaling in C57BL/KsJ-db/db mice.
Figure 4: Effects of the JNK-inhibitory peptide JIP-1-HIV-TAT-FITC on glucose tolerance and insulin resistance in C57BL6 mice treated with a high-fat, high-sucrose diet.

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Acknowledgements

This work was supported in part by grants from the Ministry of Education of Japan (to Y.Y.). We thank Y. Sasaki for her technical assistance, C. Yokogawa for her secretarial assistance and H.A. Popiel for comments on the manuscript.

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Correspondence to Hideaki Kaneto.

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Kaneto, H., Nakatani, Y., Miyatsuka, T. et al. Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide. Nat Med 10, 1128–1132 (2004). https://doi.org/10.1038/nm1111

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