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

2015 ◽  
Vol 308 (12) ◽  
pp. E1043-E1055 ◽  
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.

scholarly journals Metabolically Active Brown Adipose Tissue Is Found in Adult Subjects with Type 1 Diabetes

2019 ◽  
Vol 20 (23) ◽  
pp. 5827 ◽  
Author(s):  
Eriksson ◽  
Selvaraju ◽  
Berglund ◽  
Espes
Keyword(s):  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Control ◽  
Metabolic Activity ◽  
Glucose Utilization ◽  
Insulin Requirements ◽  
Brown Adipose

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.

scholarly journals The IL-1βReceptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Helena Cucak ◽  
Gitte Hansen ◽  
Niels Vrang ◽  
Torben Skarsfeldt ◽  
Eva Steiness ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Interleukin 1 ◽  
Nod Mice ◽  
Small Peptide ◽  
Nonobese Diabetic ◽  
Onset Of Diabetes ◽  
Diabetes Progression ◽  
Nonobese Diabetic Mice

The cytokine interleukin-1β(IL-1β) is known to stimulate proinflammatory immune responses and impairβ-cell function and viability, all critical events in the pathogenesis of type 1 diabetes (T1D). Here we evaluate the effect of SER140, a small peptide IL-1βreceptor antagonist, on diabetes progression and cellular pancreatic changes in female nonobese diabetic (NOD) mice. Eight weeks of treatment with SER140 reduced the incidence of diabetes by more than 50% compared with vehicle, decreased blood glucose, and increased plasma insulin. Additionally, SER140 changed the endocrine and immune cells dynamics in the NOD mouse pancreas. Together, the data suggest that SER140 treatment postpones the onset of diabetes in female NOD mice by interfering with IL-1βactivated pathways.

scholarly journals Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes Onset

2007 ◽  
Vol 81 (12) ◽  
pp. 6446-6458 ◽  
Author(s):  
Kate L. Graham ◽  
Joanne A. O'Donnell ◽  
Yan Tan ◽  
Natalie Sanders ◽  
Emma M. Carrington ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Young Adult ◽  
Infectious Virus ◽  
Nod Mice ◽  
Islet Autoimmunity ◽  
Adult Mice ◽  
Nonobese Diabetic ◽  
Diabetes Development ◽  
Nonobese Diabetic Mice

ABSTRACT Rotaviruses have been implicated as a possible viral trigger for exacerbations in islet autoimmunity, suggesting they might modulate type 1 diabetes development. In this study, the ability of rotavirus strain RRV to infect the pancreas and affect insulitis and diabetes was examined in nonobese diabetic (NOD) mice, an experimental model of type 1 diabetes. Mice were inoculated either orally or intraperitoneally as infants or young adults. In infant mice inoculated orally, rotavirus antigen was detected in pancreatic macrophages outside islets and infectious virus was found in blood cells, pancreas, spleen, and liver. Extraintestinal RRV spread and pancreatic presence of infectious virus also occurred in intraperitoneally inoculated infant and adult mice. The initiation of insulitis was unaltered by infection. The onset of diabetes was delayed in infant mice inoculated orally and infant and adult mice inoculated intraperitoneally. In contrast, adult mice inoculated orally showed no evidence of pancreatic RRV, the lowest rate of detectable RRV replication, and no diabetes modulation. Thus, the ability of RRV infection to modulate diabetes development in infant and young adult NOD mice was related to the overall extent of detectable virus replication and the presence of infectious virus extraintestinally, including in the pancreas. These studies show that RRV infection of infant and young adult NOD mice provides significant protection against diabetes. As these findings do not support the hypothesis that rotavirus triggers autoimmunity related to type 1 diabetes, further research is needed to resolve this issue.

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