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WSU breakthrough research of essential molecule reveals important targets in diabetes and obesity

June 27, 2013

Insulin promotes the storage and synthesis of lipids, protein and carbohydrates, and inhibiting their breakdown and release into the circulatory system. It also plays a major role in stimulating glucose entry into muscle tissue, where the glucose is metabolized and removed from the blood following meals. But gaps exist in understanding the precise molecular mechanisms by which insulin regulates glucose uptake in fat and muscle cells. A research team led by Assia Shisheva, professor of physiology in Wayne State University's School of Medicine, has made breakthrough advancements on a molecule that may provide more answers to this mystery. The conserved phospholipid enzyme, PIKfyve, was discovered in Shisheva's lab in 1999. Based on studies in cultured cells, the lab has implicated PIKfyve in the insulin-regulated glucose transport activation, which led to the development of a unique mouse model with PIKfyve ablation, or removal, in muscle (MPlfKO), the tissue responsible for the majority of postprandial glucose disposal. "Our team found a striking metabolic phenotype in the MPIfKO mice consisting of glucose intolerance and insulin resistance at an early age and on a normal diet," Shisheva said. "We also revealed that PIKfyve is essential for normal insulin signaling to GLUT4/glucose transport in muscle and provided the first in vivo evidence for the central role of PIKfyve in the mechanisms regulating healthy blood glucose levels, or glucose homeostasis."