In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue
In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue
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DOI：
10.1152/ajpendo.00488.2012
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发表时间：
2013-04-01
影响因子：
5.1
通讯作者：
Morton, Gregory J.
中科院分区：
文献类型：
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作者：
Matsen, Miles E.;Thaler, Joshua P.;Morton, Gregory J.
Me Matsen，Thaler JP，Wisse Be，Guyenet SJ，Meek Th，Ogimoto K，Cubelo A，Fischer JD，Kaiyala KJ，Schwartz MW，Morton GJ。在未控制的糖尿病中，甲状腺激素和交感神经激活剂在不增加棕色脂肪组织葡萄糖摄取的情况下诱导产热。Am J生理学内分泌Metab 304：E734-E746,2013。2013年2月5日首次出版；DOI：10.1152/ajpendo.00488.2012。-人类棕色脂肪组织(BAT)成像技术的最新进展重新引起了人们对识别BAT激活剂治疗肥胖症和糖尿病的兴趣。在未控制的糖尿病(UDM)中，BAT的激活与侧脑室(ICV)注射瘦素(Leptin)介导的降糖有关，瘦素可使链脲佐菌素(STZ)诱导的糖尿病大鼠的血糖水平正常化。脑室注射瘦素增加STZ-糖尿病患者BAT葡萄糖摄取的有效作用伴随着降低的血浆甲状腺激素(T-4)水平和BAT解偶联蛋白-1(Ucp1)mRNA水平恢复到非糖尿病对照组。因此，我们试图确定甲状腺激素受体的激活本身是否足以降低STZ-糖尿病患者的血糖水平，以及这种影响是否涉及BAT的激活。我们发现，尽管全身应用甲状腺激素(TR)β选择性激动剂GC-1增加了STZ糖尿病大鼠的能量消耗，并诱导了进一步的体重减轻，但它既没有增加BAT葡萄糖摄取，也没有减轻糖尿病高血糖。即使当GC-1与β(3)-肾上腺素能受体激动剂联合使用来模拟交感神经系统激活时，STZ糖尿病大鼠的葡萄糖摄取没有增加，血糖也没有降低，但这种干预有效地激活了BAT。在用活性甲状腺激素(T-3)代替GC-1治疗的动物中也观察到了类似的结果。综上所述，我们的数据表明，无论是恢复正常的血浆甲状腺激素水平还是激活BAT都不会对糖尿病高血糖产生任何影响，在BAT中，Ucp1基因表达的增加和葡萄糖摄取的增加在这种情况下很容易相互分离。
Matsen ME, Thaler JP, Wisse BE, Guyenet SJ, Meek TH, Ogimoto K, Cubelo A, Fischer JD, Kaiyala KJ, Schwartz MW, Morton GJ. In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue. Am J Physiol Endocrinol Metab 304: E734-E746, 2013. First published February 5, 2013; doi: 10.1152/ajpendo.00488.2012.-Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T-4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)beta-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a beta(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T-3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.