DIABETES AND METABOLIC SYNDROME • HEART FAILURE • CANCER • DATA ANALYTICS • ENTREPRENEURSHIP

Diabetes and Metabolic Syndrome

Diabetes Type II Diabetes (T2DM) and the Metabolic Syndrome (MS) are global epidemics of chronic disease. Pancreatic function is central to the development of T2DM and patients exhibit long-term hyperinsulinemia as the pancreas compensates for nutrient overload through insulin over-production. Beta cell exhaustion, insulin resistance and diabetes follow this chronic hyperinsulinemia. Transient Receptor Potential (TRP) cation channels are known targets in several aspects of the metabolic syndrome (e.g., cardiovascular disease) and TRPA1 is a possibly compelling target in diabetes since natural product agonists of TRPA1 have some efficacy in control of glycemia (e.g., using the dietary supplements allicin, cinnamaldehyde) and one prior study has shown in vitro that TRPA1 regulates insulin secretion from pancreatic cell lines and primary beta cells.

However, significant knowledge gaps remain:

(1) Is TRPA1 a viable target in diabetes and would potent non-natural product ligands show improved therapeutic gains over dietary supplements?

(2) What is the underlying mechanism by which TRPA1 is coupled to control of glycemia at the cellular and tissue level?

The PI is a member of the Diabetes Center of Biomedical Research Excellence (COBRE) at the University of Hawai'i and collaborates with leading TRP channel biologist Dr. Yasuo Mori (University of Kyoto). PI Stokes has a suite of papers, and an issued US patent, on therapeutic targeting of TRP channels in complex diseases such as heart failure. A new COBRE project on diabetes and TRPA1 by the PI has yielded interesting preliminary data.