Isolation and Characterization of Low Molecular Weight Compounds Derived from Plant Extracts that Activate the IRS-2 Dependent Insulin Signaling Cascade.

DESCRIPTION provided by applicant This is a Phase I SBIR Application entitled andquot Isolation and Characterization of Low Molecular Weight Compounds Derived from Plant Extracts that Activate the IRS Dependent Insulin Signaling Cascade andquot Diabetes is a growing and significant global health concern Insulin Receptor Substrate IRS is a critical component in the insulin mediated signal transduction cascade which regulates glucose and lipid metabolism insulin sensitivity and the growth function and survival of insulin producing beta cells Molecules that activate IRS have the potential to help maintain glucose metabolism increase insulin sensitivity and increase insulin secretion by enhancing the function and viability of cells HPRL previously developed an IRS specific assay system to identify leads that activate ectopically overproduced IRS in DIRS cells while having no effect on control D cells which lack detectable IRS Using this cell based assay we have discovered novel plant extracts that activate IRS signaling in DIRS cells HPRL has filed patents describing plant extracts with insulin like IRS activating pharmacological properties One of these plant extracts now designated HP activates the IRS signal transduction cascade HP exhibits of the IRS signaling activity as compared to Insulin in cell based assays in vitro Preliminary in vivo efficacy and safety data for this extract in mice demonstrate that HP is at least as effective as metformin in a short term studies SBIR funding is requested to enable the isolation and characterization one or more of the active natural product compounds from HP that activate IRS signaling In Phase II we intend to further investigate the safety and efficacy of the isolated natural product compounds with a goal of developing a therapeutic treatment for diabetes and related metabolic disorders Compounds isolated from HP will comprise a significant and innovative new area of therapeutic discovery with great potential to treat and possibly even prevent metabolic disorders such as diabetes PUBLIC HEALTH RELEVANCE Isolation and Characterization of Low Molecular Weight Compounds Derived from Plant Extracts that Activate the IRS Dependent Insulin Signaling Cascade