Subhadra Gunawardana, PhD
Associate Professor, Cell Biology and Physiology
Washington University in St. Louis (WU)
Novel techniques for correcting type-1 diabetes without insulin, utilizing the beneficial effects of healthy adipose tissue: The ultimate goal in treating type 1 diabetes is to restore glucose homeostasis. Our research shows that glucose homeostasis can be achieved without insulin, through transplantation of embryonic brown adipose tissue (BAT) in the subcutaneous space. In mouse models of T1D chemically or autoimmune induced, BAT transplants result in weight gain, marked decrease of inflammation, and regeneration of new healthy subcutaneous white adipose tissue (WAT), accompanied by euglycemia and reversal of clinical diabetes. These effects are independent of insulin. Both plasma insulin levels and pancreatic insulin content post-mortem remain drastically low, comparable to untreated diabetic control mice. There are progressive increases in adipose tissue derived hormones such as adiponectin, leptin and IGF-1, marked suppression of glucagon, and progressive decreases in pro-inflammatory cytokines such as IL-6 and MCP-1. Together, these data suggest a new equilibrium of physiologically generated hormones that compensate for the lack of insulin.
While all the players in this equilibrium are not identified, preliminary data suggest the involvement of several factors, with a critical role for IGF-1. To translate this approach towards a therapy for human patients, we are exploring suitable alternatives for embryonic BAT, such as healthy adult adipose tissue transplants temporarily supplemented with embryonic growth factors or anti-inflammatory agents.