Cell-Permeable Peptide Inhibitor of c-Jun NH2-Terminal Kinase for the Treatment of Diabetes

Hirofumi      Noguchi

Abstract

Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. A variety of peptides, known as protein transduction domains (PTDs) or cell-penetrating peptides (CPPs), have been recently characterized for their ability to translocate into live cells. Some studies have shown that this technology is useful for the treatment of diabetes. In islet isolation and transplantation, cell-permeable peptides deliver anti-apoptotic molecules such as inhibitors of the c-Jun NH2-terminal kinases (JNKs) to protect islets. In type 2 diabetes, a cell-permeable peptide of JNK inhibitor markedly improves insulin resistance and ameliorates glucose tolerance in diabetic mice. JNKs are classic stress-activated protein kinases and many cellular stresses have been shown to stimulate JNK activation. In this review, we show some of the most recent contributions to the advancement of knowledge of the JNK pathway and several possibilities for the treatment of diabetes using protein transduction technology and the JNK inhibitory peptide.

Keywords: Diabetes, c-Jun NH2-terminal kinase, JNK inhibitor, protein transduction technology, cell-permeable peptide, cell penetrating peptide, islet transplantation, apoptosis