Metabolic Regulation and Obesity
Signal Transduction/Hormone Action
Category(ies) of Research
Descriptor of Research
The major focus of my research is to develop better therapeutic approaches for Type 1 Diabetes (T1D), without the limitations involved in islet/pancreas transplantation. Subcutaneous transplantation of embryonic brown adipose tissue (BAT) has proven effective in reversing T1D independent of insulin. BAT transplants produce rapid and long-lasting euglycemia in mouse models of T1D both chemically and autoimmune induced, with no need for immunosuppression. Return to normoglycemia correlates with replenishment of healthy white adipose tissue, increased levels of beneficial adipokines and overall decrease of inflammation, while insulin remains consistently low. Thus, it appears that a new physiological equilibrium of adipose tissue-derived factors compensates for the lack of insulin. Recent data suggest a role for insulin-like growth factor (IGF-1), both in the early survival and continued function of BAT transplants. Temporary supplementation with IGF-1 enables adult BAT transplants to produce long-term euglycemia. Ongoing work seeks to document the underlying mechanisms of metabolic regulation following BAT transplants, and to customize this approach for human patients through establishing suitable alternatives for embryonic tissue.