A single protein can 'sense' fasting signals and a potentially damaging form of cellular stress. Revealed in Nature, the discovery has implications for our understanding of glucose regulation and obesity.
Glucose production in the liver of fasted mammals is triggered by the pancreatic-produced hormone glucagon, a process part-regulated by a protein called CRTC2. Here, Marc Montminy and colleagues show that CRTC2 functions as a dual sensor in the liver for both fasting signals and a stress response generated by a cellular organelle called the endoplasmic reticulum (ER). Chronic ER stress is already known to have a role in glucose regulation, boosting the production of the sugar in the liver, and promoting insulin resistance in obese individuals. Here, the team show that cross-talk between fasting and ER stress pathways contributes to glucose homeostasis under lean conditions, and also to the development of high blood sugar levels in obesity. CONTACT Marc Montminy (Salk Institute, La Jolla, CA, USA) E-mail: montminy@salk.edu Abstract available online. (C) Nature press release.
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