Baranwal Aparna, Mirbolooki M Reza, Mukherjee Jogeshwar
Mol Imaging. 2015;14(12):22-33. doi: 10.2310/7290.2015.00028.
Metabolic activity of brown adipose tissue (BAT) is activated by β3-adrenoceptor agonists and norepinephrine transporter (NET) blockers and is measurable using [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) in rats. Using the streptozotocin (STZ)-treated rat model of type 1 diabetes mellitus (T1DM), we investigated BAT activity in this rat model under fasting and nonfasting conditions using [(18)F]FDG PET/CT. Drugs that enhance BAT activity may have a potential for therapeutic development in lowering blood sugar in insulin-resistant diabetes. Rats were rendered diabetic by administration of STZ and confirmed by glucose measures. [(18)F]FDG was injected in the rats (fasted or nonfasted) pretreated with either saline or β3-adrenoceptor agonist CL316,243 or the NET blocker atomoxetine for PET/CT scans. [(18)F]FDG metabolic activity was computed as standard uptake values (SUVs) in interscapular brown adipose tissue (IBAT) and compared across the different drug treatment conditions. Blood glucose levels > 500 mg/dL were established for the STZ-treated diabetic rats. Under fasting conditions, average uptake of [(18)F]FDG in the IBAT of STZ-treated diabetic rats was approximately 70% lower compared to that of normal rats. Both CL316,243 and atomoxetine activated IBAT in normal rats had an SUV > 5, whereas activation in STZ-treated rats was significantly lower. The agonist CL316,243 activated IBAT up to threefold compared to saline in the fasted STZ-treated rat. In the nonfasted rat, the IBAT activation was up by twofold by CL316243. Atomoxetine had a greater effect on lowering blood sugar levels compared to CL316,243 in the nonfasted rats. A significant reduction in metabolic activity was observed in the STZ-treated diabetic rodent model. Increased IBAT activity in the STZ-treated diabetic rat under nonfasted conditions using the β3-adrenoceptor agonist CL316,243 suggests a potential role of BAT in modulating blood sugar levels. Further studies are needed to evaluate the therapeutic role of β3-adrenoceptor agonists in insulin-resistant T1DM.
棕色脂肪组织（BAT）的代谢活性可被β3-肾上腺素能受体激动剂和去甲肾上腺素转运体（NET）阻滞剂激活，并且在大鼠中可使用[（18）F]氟脱氧葡萄糖（[（18）F]FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）进行测量。我们使用链脲佐菌素（STZ）诱导的1型糖尿病（T1DM）大鼠模型，通过[（18）F]FDG PET/CT研究了该大鼠模型在禁食和非禁食条件下的BAT活性。增强BAT活性的药物可能在治疗胰岛素抵抗性糖尿病以降低血糖方面具有治疗开发潜力。通过给予STZ使大鼠患糖尿病，并通过血糖测量进行确认。将[（18）F]FDG注射到用生理盐水或β3-肾上腺素能受体激动剂CL316,243或NET阻滞剂托莫西汀预处理的大鼠（禁食或非禁食）中，以进行PET/CT扫描。[（18）F]FDG代谢活性以肩胛间棕色脂肪组织（IBAT）中的标准摄取值（SUV）计算，并在不同药物治疗条件下进行比较。STZ处理的糖尿病大鼠的血糖水平>500mg/dL。在禁食条件下，STZ处理的糖尿病大鼠IBAT中[（18）F]FDG的平均摄取量比正常大鼠低约70％。CL316,243和托莫西汀均可激活正常大鼠的IBAT，SUV>5，而在STZ处理的大鼠中激活程度明显较低。与禁食的STZ处理大鼠中的生理盐水相比，激动剂CL316,243可将IBAT激活高达三倍。在非禁食大鼠中，CL316243可使IBAT激活增加两倍。在非禁食大鼠中，托莫西汀在降低血糖水平方面比CL316,243具有更大的作用。在STZ处理的糖尿病啮齿动物模型中观察到代谢活性显着降低。在非禁食条件下使用β3-肾上腺素能受体激动剂CL316,243增加STZ处理的糖尿病大鼠的IBAT活性，表明BAT在调节血糖水平方面具有潜在作用。需要进一步研究以评估β3-肾上腺素能受体激动剂在胰岛素抵抗性T1DM中的治疗作用。
