The innate immune system provides the first line of defense against microbial pathogens and is imperative for the survival of all multicellular organisms. A critical step in the innate immune response is the identification of common motifs from invading organisms as foreign. This discrimination relies on a family of evolutionary conserved pattern recognition receptors (PRRs) that recognize a limited, but highly conserved, set of molecular structures inherent to microbial pathogens, which upon detection mediate inflammatory responses. Emerging evidences indicate that in addition to invading pathogens, PRRs can also be activated by endogenous molecules of non-microbial origin and may also participate in the induction of sterile inflammation. Both infection-induced inflammation and sterile inflammation can lead to chronic inflammation, which is now considered as one of the key etiological conditions leading to the development of many chronic diseases, including atherosclerosis, insulin resistance and cancer. Inflammation-mediated insulin resistance has been linked to macrophage and adipose tissue cross talk, which ultimately may impair insulin action in skeletal muscle and/or the liver leading to whole body insulin resistance. Since, the components of the innate immune system are ubiquitous expressed, a cell autonomous response is possible to external stimuli to induce inflammatory response. We are exploring the role of PRRs in the pathogenesis of tissue specific insulin resistance. Activation of innate immunity provides a new model for the pathogenesis of type-2 diabetes and the metabolic syndrome, which may explain some or all of these features, and points to research directions that might result in new therapeutic approaches for managing and predicting type-2 diabetes and its complications.

Type 2 diabetes is a global health priority. Insulin resistance is the major defect underlying the development of type 2 diabetes and metabolic syndrome. Insulin resistance is characterized by impaired insulin-stimulated disposal of glucose in skeletal muscle, adipose and other peripheral tissues due to defect in translocation of insulin sensitive glucose transporter-4 (GLUT-4) from intracellular compartment to plasma membrane. There has been considerable interest in insulin-sensitizing agents to counteract insulin resistance and interventions with ability to stimulate GLUT-4 translocation might be useful for the treatment of the disease.

Here, we are investigating plant derived molecule with ability to modulate GLUT-4 translocation leading to increased insulin sensitivity. We have proposed a targeted approach to investigate the active chemical molecule/s with ability to counteract insulin resistance from plants and optimize their biological efficacy by chemistry-based approaches and to investigate the underlying molecular mechanism of action and in vivo confirmation of biological efficacy of identified molecule/s.