Taking a closer look at our on/off relationship with insulin

2012

Challenge

Diabetes now affects more than 25 million people of all ages Fast Facts on Diabetes, yet the molecular underpinnings of the disease remain unclear. Although the overall pathways that drive the production of insulin are known, the molecular mechanisms that control rapid changes in insulin synthesis—for example following a meal—are not.

Advance

IRP investigators led by Eun Kyung Lee, Ph.D., identified a previously unknown component of the pathway—an RNA-binding protein named HuD, expressed in pancreatic β cells—that can bind insulin mRNA and inhibit its translation into protein, essentially blocking its production. The researchers also showed that, in response to increased glucose levels, HuD releases insulin mRNA, allowing the production of insulin protein.

Impact

The discovery that an RNA-binding protein can repress insulin translation in a rapidly reversible manner suggests that deficiencies in this protein could underlie some cases of diabetes. Work is underway to systematically compare HuD in the pancreatic β cells of diabetic and non-diabetic subjects, with the aim of determining if HuD could be a new therapeutic target.

Publications

Lee EK, Kim W, Tominaga K, Martindale JL, Yang X, Subaran SS, Carlson OD, Mercken EM, Kulkarni RN, Akamatsu W, Okano H, Perrone-Bizzozero NI, de Cabo R, Egan JM, Gorospe M. (2012). RNA-binding protein HuD controls insulin translation. Mol Cell. 45(6), 826-35.