Review
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Diabetes. Jul 15, 2011; 2(7): 114-118
Published online Jul 15, 2011. doi: 10.4239/wjd.v2.i7.114
Unravelling the story of protein misfolding in diabetes mellitus
Sally E Thomas, Lucy Dalton, Elke Malzer, Stefan J Marciniak
Sally E Thomas, Lucy Dalton, Elke Malzer, Stefan J Marciniak, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB0 2XY, United Kingdom
Author contributions: All authors contributed equally to this editorial.
Supported by a PhD studentship form Diabetes UK (for Thomas SE)
Correspondence to: Stefan J Marciniak, MA, FRCP, PhD, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB0 2XY, United Kingdom. sjm20@cam.ac.uk
Telephone: +44-1223-762660 Fax: +44-1223-336827
Received: January 15, 2011
Revised: June 30, 2011
Accepted: July 7, 2011
Published online: July 15, 2011
Abstract

Both environmental and genetic factors contribute to the development of diabetes mellitus and although monogenic disorders are rare, they offer unique insights into the fundamental biology underlying the disease. Mutations of the insulin gene or genes involved in the response to protein misfolding cause early onset diabetes. These have revealed an important role for endoplasmic reticulum stress in β-cell survival. This form of cellular stress occurs when secretory proteins fail to fold efficiently. Of all the professional secretory cells we possess, β-cells are the most sensitive to endoplasmic reticulum stress because of the large fluctuations in protein synthesis they face daily. Studies of endoplasmic reticulum stress signaling therefore offer the potential to identify new drug targets to treat diabetes.

Keywords: Endoplasmic reticulum stress; Diabetes; Unfolded protein response; PKR-like ER kinase