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      Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant.

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          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 nonobese 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 the 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-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I 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-I as a likely mediator in the resulting equilibrium.

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          Author and article information

          Journal
          Am. J. Physiol. Endocrinol. Metab.
          American journal of physiology. Endocrinology and metabolism
          1522-1555
          0193-1849
          Jun 15 2015
          : 308
          : 12
          Affiliations
          [1 ] Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee subhadra.gunawardana@vanderbilt.edu.
          [2 ] Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
          Article
          ajpendo.00570.2014
          10.1152/ajpendo.00570.2014
          25898954
          aa7462ec-5304-407d-9769-083264c82cd4
          Copyright © 2015 the American Physiological Society.
          History

          brown adipose tissue,insulin independent,insulin-like growth factor I,transplantation,type 1 diabetes

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