Science for Life Laboratory, Department of Medicinal Chemistry, Division of Molecular Imaging, Uppsala University, 75123 Uppsala, Sweden.
Turku PET Centre, Åbo Akademi, Turku 20520, Finland.
Int J Mol Sci. 2019 Nov 20;20(23):5827. doi: 10.3390/ijms20235827.
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 ( = 11) by 2-deoxy-2-(F)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 × 100 g. The glucose utilization per gram tissue was higher in BAT when compared with both WAT ( = 0.049) and skeletal muscle ( = 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.
1 型糖尿病(T1D)的特征是胰岛素产生细胞的丧失,因此胰岛素分泌和代谢控制受损。除胰岛素外,还有许多激素和细胞因子影响代谢,其中许多激素和细胞因子可以从棕色脂肪组织(BAT)中分泌出来。然而,尽管临床前研究表明,在 T1D 小鼠模型中移植 BAT 可以恢复代谢控制,但 T1D 患者 BAT 的存在和活性尚未得到研究。通过冷刺激后 2-脱氧-2-(F)氟-D-葡萄糖 PET/CT,研究了 11 名 T1D 患者(= 11)的 BAT、白色脂肪组织(WAT)和骨骼肌的代谢活性。在 11 名 T1D 患者中有 4 名(患病率为 36%)检测到功能性 BAT。锁骨 BAT 区域的葡萄糖利用率范围为 0.75-38.7 µmol×min×100 g。与 WAT(= 0.049)和骨骼肌(= 0.039)相比,BAT 每克组织的葡萄糖利用率更高。然而,没有发现 BAT 活性与代谢控制或胰岛素需求之间存在相关性。总之,这是首次在 T1D 患者中检测到冷诱导的 BAT,其代谢活性范围很广。与动物模型的研究结果相反,在正常生理条件下,BAT 的代谢活性对 T1D 患者的胰岛素需求或代谢控制几乎没有影响。