doi:10.1038/nindia.2015.143 Published online 26 October 2015
Researchers have identified a novel way of how inflammation may lead to insulin resistance. They have identified PRIP-interacting protein with methyltransferase domain (PMIT) as a new player in stress-induced Type 2 diabetes (T2D)1.
Responsiveness to the gluco-regulatory hormone insulin, known as insulin sensitivity, is impaired years before the onset of T2D. Chronic low-grade inflammation ensuing a long term high fat diet is known to be responsible for this. However, the underlying reasons were inadequately understood.
Researchers from Hyderabad-based Dr. Reddy's Institute of Life Sciences and University of Hyderabad; Nirma University, Ahmedabad; and Northwestern University, Chicago, USA used cultured muscle cells and animal models to understand the reasons better. They showed that a co-activator binding protein PIMT/TGS1 mediates the effects of inflammation induced insulin unresponsiveness in skeletal muscle.
PIMT does this by abolishing the expression of a protein GLUT4 which transports glucose from the blood stream into skeletal muscle, a major organ involved in glucose metabolism. The researchers also found that addition of a phosphate group at a specific position of PIMT (Ser298) may serve as a trigger to turn on the ability of PIMT to promote insulin resistance.
“The findings from this study will likely pave way for the development of novel therapeutic strategies for T2D,” they report.
1. Kain, V. et al. Co-activator binding protein PIMT mediates TNF-α induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4. Sci. Rep. 5 (2015) doi: 10.1038/srep15197