New Publication for Piston Lab
Congratulations to Suba Gunawardana and David Piston on their new publication in the American Journal of Physiology - Endocrinology and Metabolism.
Gunawardana, SC, Piston, DW. (2015) Insulin-independent reversal of type 1 diabetes in non-obese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab. [E-published April 21, doi: 10.1152/ajpendo.00570.2014]
Abstract: Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation, and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically-induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In non-obese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and long-lasting euglycemia. In addition, BAT transplants placed prior to onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin, and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulin-like growth factor-1 (IGF-1) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-1 compared with little or no expression in controls, and plasma IGF-1 levels show a direct negative correlation with glucose, glucagon and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-1 may stimulate regeneration of new healthy white adipose tissue, which in turn secrete hypoglycemic adipokines that substitute for insulin. IGF-1 can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants, and implicate IGF-1 as a likely mediator in the resulting equilibrium.