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. The subcutaneous space provides a safer and less invasive alternative to traditional transplant sites, and subcutaneous transplantation of embryonic pancreatic tissue has proved successful in correcting T1D in certain immune-deficient mouse strains. Curiously, reversal of diabetes in this situation occurs without an accompanying improvement in insulin response, but an increase in adipose tissue hormones instead. Based on these intriguing observations, I explored novel approaches to correct T1D independent of insulin. Subcutaneous transplantation of embryonic brown adipose tissue (BAT) has proved remarkably successful in correcting T1D without insulin in immune-competent as well as immune-deficient mice. Euglycemia is accompanied by robust proliferation of white adipose tissue (WAT) and significant decrease of inflammation. While insulin remains consistently subnormal, there is a progressive increase in several hypoglycemic adipokines, and suppression of glucagon. Thus it appears that alternative hormones from the BAT transplant, newly-formed WAT, and possibly the endogenous BAT establish a new equilibrium that leads to glucose homeostasis. My current work seeks to document the underlying mechanisms of insulin-independent glycemic regulation following BAT transplants; to delineate the relationship between BAT function and inflammation; and to refine this approach for potential translation to clinical settings.
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Key: MeSH Term KeywordAdipose Tissue, Brown Adipose Tissue, White Amino Acids, Cyclic Analysis of Variance Arginine Brown adipose tissue Case-Control Studies Cells, Cultured Cell Survival Colon Diabetes Mellitus, Experimental Disease Models, Animal Dog Diseases Drug Synergism Enzyme Activation Green Fluorescent Proteins Humans insulin-indepentdent Intestinal Mucosa Intracellular Fluid Ketoglutaric Acids Mice Peroxidase Rats Receptor, Insulin Skin Sodium-Calcium Exchanger Stimulation, Chemical Transcription Factors Transplantation Transplantation, Heterotopic Type 1 diabetes Up-Regulation Weight Gain White adipose tissue