» Articles » PMID: 25898954

Insulin-independent Reversal of Type 1 Diabetes in Nonobese Diabetic Mice with Brown Adipose Tissue Transplant

Overview
Date 2015 Apr 23
PMID 25898954
Citations 49
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Adipokines in the Crosstalk between Adipose Tissues and Other Organs: Implications in Cardiometabolic Diseases.

Hemat Jouy S, Mohan S, Scichilone G, Mostafa A, Mahmoud A Biomedicines. 2024; 12(9).

PMID: 39335642 PMC: 11428859. DOI: 10.3390/biomedicines12092129.


The role of brown adipose tissue in mediating healthful longevity.

Zhang J, Kibret B, Vatner D, Vatner S J Cardiovasc Aging. 2024; 4(2).

PMID: 39119146 PMC: 11309368. DOI: 10.20517/jca.2024.01.


Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies.

Cheng Y, Liang S, Zhang S, Hui X Biomedicines. 2024; 12(7).

PMID: 39062047 PMC: 11275133. DOI: 10.3390/biomedicines12071474.


Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.

Dewal R, Yang F, Baer L, Vidal P, Hernandez-Saavedra D, Seculov N iScience. 2024; 27(2):108927.

PMID: 38327776 PMC: 10847743. DOI: 10.1016/j.isci.2024.108927.


Sweet triterpenoid glycoside from ameliorates obesity-induced insulin resistance through inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway.

Li J, He J, He H, Wang X, Zhang S, He Y Curr Res Food Sci. 2024; 8:100677.

PMID: 38303998 PMC: 10831159. DOI: 10.1016/j.crfs.2024.100677.


References
1.
Ghosh M, Gorantla V, Makena P, Luellen C, Sinclair S, Schwingshackl A . Insulin-like growth factor-I stimulates differentiation of ATII cells to ATI-like cells through activation of Wnt5a. Am J Physiol Lung Cell Mol Physiol. 2013; 305(3):L222-8. PMC: 3743013. DOI: 10.1152/ajplung.00014.2013. View

2.
Ouchi N, Parker J, Lugus J, Walsh K . Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11(2):85-97. PMC: 3518031. DOI: 10.1038/nri2921. View

3.
Cypess A, Kahn C . Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes. 2010; 17(2):143-9. PMC: 3593105. DOI: 10.1097/MED.0b013e328337a81f. View

4.
Schneck A, Iannelli A, Patouraux S, Rousseau D, Bonnafous S, Bailly-Maitre B . Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake, white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots. Surg Endosc. 2013; 28(2):592-602. DOI: 10.1007/s00464-013-3211-1. View

5.
Gannon M, Nuttall F . Effect of a high-protein diet on ghrelin, growth hormone, and insulin-like growth factor-I and binding proteins 1 and 3 in subjects with type 2 diabetes mellitus. Metabolism. 2011; 60(9):1300-11. DOI: 10.1016/j.metabol.2011.01.016. View