Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice

Abstract

Pancreatic disorders: when protein modification misfires Reduced levels of a protein called Cosmc in the pancreas may lead to pancreatic disorders and a rare form of diabetes. Disruption to glycosylation, the process by which carbohydrates are added to proteins, can have significant knock-on effects for cellular functioning. Gerrit Wolters-Eisfeld at the University Medical Center Hamburg-Eppendorf, Germany, and co-workers used mouse models to demonstrate the importance of correct formation of one type of carbohydrate, O-glycans, for normal pancreatic function. The team generated mice without Cosmc, a molecule that assists with O-glycosylation. Loss of Cosmc in the pancreas resulted in shortened O-glycans and pancreatic insufficiency. However, one protein called Cel was modified in abundance; this may be further bad news because mutations in Cel are linked to the onset of a rare form of diabetes.