Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing cells and hence insulin secretion and metabolic control. In addition to insulin, there are a number of hormones and cytokines that influence metabolism, and many of these can be secreted from brown adipose tissue (BAT). However, the presence and activity of BAT in T1D have not been studied, despite the fact that preclinical studies have shown that transplantation of BAT in mouse models of T1D can restore metabolic control. The metabolic activity of BAT, white adipose tissue (WAT), and skeletal muscle was investigated in patients with T1D (n = 11) by 2-deoxy-2-(18F)fluoro-D-glucose PET/CT after cold stimulation. Functional BAT was detected in 4 out of 11 individuals with T1D with a prevalence of 36%. The glucose utilization rate in the supraclavicular BAT regions ranged from 0.75–38.7 µmol × min−1 × 100 g−1. The glucose utilization per gram tissue was higher in BAT when compared with both WAT (p = 0.049) and skeletal muscle (p = 0.039). However, no correlation between BAT activity and metabolic control or insulin requirements was found. In conclusion, for the first time, cold-induced BAT was detected in patients with T1D with a wide range in metabolic activity. Contrary to findings in animal models, the metabolic activity of BAT had negligible impact on insulin requirements or metabolic control in T1D under normal physiological conditions.

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Insulin-Independent Reversal of Type-1 Diabetes Following Transplantation of Adult Brown Adipose Tissue Supplemented With IGF-1

Transplantation Direct ◽

10.1097/txd.0000000000000945 ◽

2019 ◽

Vol 5 (11) ◽

pp. e500 ◽

Cited By ~ 2

Author(s):

Subhadra C. Gunawardana ◽

David W. Piston

Keyword(s):

Type 1 Diabetes ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00570.2014 ◽

2015 ◽

Vol 308 (12) ◽

pp. E1043-E1055 ◽

Cited By ~ 45

Author(s):

Subhadra C. Gunawardana ◽

David W. Piston

Keyword(s):

Type 1 Diabetes ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Nod Mice ◽

Nonobese Diabetic ◽

Brown Adipose ◽

Igf I ◽

Onset Of Diabetes ◽

Nonobese Diabetic Mice

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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Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

Hormone and Metabolic Research ◽

10.1055/a-0919-3879 ◽

2019 ◽

Vol 51 (10) ◽

pp. 671-677 ◽

Cited By ~ 7

Author(s):

Maurício Martins da Silva ◽

Carlos Frederico Lima Gonçalves ◽

Leandro Miranda-Alves ◽

Rodrigo Soares Fortunato ◽

Denise P. Carvalho ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Bisphenol A ◽

Brown Adipose Tissue ◽

Tissue Type ◽

Deiodinase Activity ◽

Brown Adipose

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

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Nicotine suppresses energy storage through activation of sympathetic outflow to brown adipose tissue via corticotropin-releasing factor type 1 receptor

Neuroscience Letters ◽

10.1016/j.neulet.2009.03.054 ◽

2009 ◽

Vol 455 (1) ◽

pp. 26-29 ◽

Cited By ~ 15

Author(s):

Asuka Mano-Otagiri ◽

Azusa Iwasaki-Sekino ◽

Hisayuki Ohata ◽

Keiko Arai ◽

Tamotsu Shibasaki

Keyword(s):

Adipose Tissue ◽

Energy Storage ◽

Brown Adipose Tissue ◽

Corticotropin Releasing Factor ◽

Sympathetic Outflow ◽

Brown Adipose ◽

Factor Type

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Deiodinase Activities in Thyroids and Tissues of Iodine-Deficient Female Rats

Endocrinology ◽

10.1210/en.2012-1727 ◽

2013 ◽

Vol 154 (1) ◽

pp. 529-536 ◽

Cited By ~ 25

Author(s):

Rosalia Lavado-Autric ◽

Rosa Maria Calvo ◽

Raquel Martinez de Mena ◽

Gabriella Morreale de Escobar ◽

Maria-Jesus Obregon

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Cerebral Cortex ◽

Brown Adipose Tissue ◽

Female Rats ◽

Iodothyronine Deiodinase ◽

Brown Adipose ◽

Type 3

Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T3 in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T3, and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T4 and T3 concentrations decreased in plasma, tissues, and thyroids of LID rats, and T4 decreased more than T3 (50%). The highest type 1 iodothyronine deiodinase (D1) activities were found in the thyroid, kidney, and the liver; pituitary, lung, and ovary had lower D1 activities; but the lowest levels were found in the heart and skeletal muscle. D1 activity decreased in all tissues of LID rats (10–40% of LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold. Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid, brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats and about 20-fold in the whole gland. D2 always increased in response to LID, and maximal increases were found in the cerebral cortex (19-fold), thyroid, brown adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression in other tissues. Our data indicate that LID induces changes in deiodinase activities, especially in the thyroid, to counteract the low T4 synthesis and secretion, contributing to maintain the local T3 concentrations in the tissues with D2 activity.

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