Grant: Discovery Grants Program - Individual

My main research program investigates how different stimuli, including hormones, control glucose homeostasis. My focus is to understand the intracellular signaling pathways that are activated and control muscle and fat tissue glucose metabolism and to find food components, nutraceuticals that modulate these signaling pathways. Insulin is a pancreatic hormone that plays an important role in glucose homeostasis. Insulin binds to its receptor found on the plasma membrane of skeletal muscle and fat cells and activates the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway causing translocation of intracellularly stored glucose transporters proteins (GLUT4) to the plasma membrane resulting in increased glucose uptake and metabolism. Defects or impairments in the PI3K-Akt signaling pathway lead to inability of insulin to act on skeletal muscle and fat tissues, a condition termed insulin resistance. Activation of another signaling cascade, the AMP-activated protein kinase (AMPK) cascade in insulin target tissues also leads to increased glucose uptake and metabolism. The AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular energy sensor and becomes activated in response to increased AMP/ATP ratio. Importantly, AMPK is activated by exercise/contraction, and various compounds including the drug metformin which is used to treat individuals with increased blood glucose levels and insulin resistance. In recent years, activation of AMPK has been viewed as a targeted approach to regulate glucose homeostasis. My work on the intracellular signaling mechanisms controlling glucose uptake and metabolism has led me to search for compounds that can modulate these intracellular pathways. Studies from my lab indicate that the compounds/polyphenols carnosic acid (CA), rosmarinic acid and carnosol (COH), found in rosemary, strongly activate AMPK, influence these signaling pathways and alter tissue metabolism in ways that might be beneficial to people who suffer from insulin resistance. The long-term goals of the proposed research program are to understand glucose homeostasis and investigate the effects of the plant-derived chemicals CA, RA and COH on fundamental cellular mechanisms involved in insulin resistance. These goals will be addressed using cells in culture (in vitro) and animal models of insulin resistance and hyperglycemia. The knowledge gained from the proposed studies will be applied towards the development of a desired nutraceutical against insulin resistance. Many Canadians suffer from insulin resistance and hyperglycemia. My research focused on investigating the cellular mechanism of these conditions and finding nutraceuticals to modify them will provide huge benefit to the Canadian society. Moreover, the proposed research program will provide students with training opportunities in advanced technical skillsets, research experience and leadership that will benefit research and industry in Canada.