GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation
A new Journal of Clinical Investigation paper from Patrik Rorsman‘s group provides key insights into signaling mechanisms of GLP-1, a peptide that enhances insulin secretion and is the basis of many diabetes drugs. Type 2 diabetes affects about 350 million individuals in the world, and is the focus of intensive research. Montana Molecular’s DAG sensors play an important role in diabetes research. In this particular project, the value of measuring multiple signaling pathways in pancreatic islets to gain a more complete understanding of diabetes drugs effects is clear.
Shigeto, Ramracheya, Tarasov, and colleagues at the Oxford Centre for Diabetes & Metabolism (OCDEM) expressed Montana Molecular’s DAG sensor in β cells and directly measured DAG activation by GLP-1 at physiologically relevant concentrations (pM). Surprising, at these low concentrations of GLP-1, the signaling cascade does not act through PKA, but through PLC/PKC to alter the TRPM4 and 5 channels, depolarizing the cells and increasing the probability of action potentials. New insights into the mechanism of GLP-1 signaling was made possible with better biosensors from Montana Molecular.
We sincerely appreciate the efforts of the Dr. Rorsman’s and his team, as early adopters of our cAMP and DAG sensors. What signaling pathways would you like to measure?
Read the full Article in J.Clin Invest:
Makoto Shigeto, Reshma Ramracheya, Andrei I. Tarasov, et al. GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation. J Clin Invest. 2015. doi:10.1172/JCI81975.