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Publication
Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with
brown adipose tissue transplant.
Authors Gunawardana SC, Piston DW
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2015
Date Published 6/1/2015
Volume : Pages 308 : E1043 - 55
PubMed Reference 25898954
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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