Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation
Regulation of metabolic activity in adipose tissue is of great concern for treating obesity. This study aimed to evaluate the adrenergic regulation of glucose uptake and the thermogenic program in adipose tissues in mouse models of both type 1 and 2 diabetes mellitus (DM).
Male mice were treated with streptozotocin to induce type 1 (T1) DM, and obese ob/ob mice were used for the type 2 (T2) DM model. After selective β3-adrenoreceptor stimulation by CL 316,243 (CL) treatment, 2-deoxy-d-[14C]glucose ([14C]DG) was administered to DM and corresponding control mice. Radioactivity and uncoupling protein 1 (UCP1) expression were measured and analyzed in adipose tissues.
In T1DM, [14C]DG uptake in brown adipose tissue (BAT) decreased both at rest and upon CL stimulation, and UCP1 expression was preserved. However, CL treatment enhanced [14C]DG uptake without impairing UCP1 expression in inguinal white adipose tissue (iWAT). In this model, CL could not alter blood glucose levels. In T2DM mice, the blood glucose level was significantly lowered by CL treatment. There was no decrease in CL-induced [14C]DG uptake in BAT, and UCP1 expression was maintained. However, [14C]DG uptake was not increased in iWAT and no UCP1 expression was observed in iWAT (browning).
The metabolic response against adrenergic stimulation varied depending on the type of adipose tissue and DM. This could be important for the therapeutic activation of adipose tissue metabolism in obese diabetic patients.
Key wordsAdipose tissue Diabetes mellitus Glucose Uncoupling protein
The authors thank Dr. Teruo Kawada (Graduate School of Agriculture, Kyoto University) for the kind gift of the anti-UCP1 antibody.
Compliance with Ethical Standards
Conflict of Interest
The authors have indicated that they have no financial conflict of interest.
- 9.Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:536–546Google Scholar
- 20.Fu L, Isobe K, Zeng Q, Suzukawa K, Takekoshi K, Kawakami Y (2008) The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice. Eur J Pharmacol 584:202–206CrossRefPubMedGoogle Scholar
- 24.Hankir MK, Kranz M, Keipert S, Weiner J, Andreasen SG, Kern M, Patt M, Klöting N, Heiker JT, Brust P, Hesse S, Jastroch M, Fenske WK (2017) Dissociation between brown adipose tissue 18F-FDG uptake and thermogenesis in uncoupling protein 1-deficient mice. J Nucl Med 58:1100–1103CrossRefPubMedGoogle Scholar
- 27.Ishino S, Sugita T, Kondo Y, Okai M, Tsuchimori K, Watanabe M, Mori I, Hosoya M, Horiguchi T, Kamiguchi H (2017) Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG. Ann Nucl Med 31:413–423CrossRefPubMedGoogle Scholar
- 33.Mattsson CL, Csikasz RI, Chernogubova E, Yamamoto DL, Hogberg HT, Amri EZ, Hutchinson DS, Bengtsson T (2011) β1-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β3-adrenergic receptor-knockout mice via nonshivering thermogenesis. Am J Physiol Endocrinol Metab 301:E1108–E1118CrossRefPubMedGoogle Scholar