Insulin-sensitizing effects of thiazolidinediones are not linked to adiponectin receptor expression in human fat or muscle
Insulin-sensitizing effects of thiazolidinediones are not linked to adiponectin receptor expression in human fat or muscle
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DOI：
10.1152/ajpendo.00312.2006
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发表时间：
2007-05-01
影响因子：
5.1
通讯作者：
Hawkins, Meredith
中科院分区：
文献类型：
--
作者：
Li, Weijie;Tonelli, Julia;Hawkins, Meredith
噻唑烷二酮（TZD）类PPAR γ激动剂可增加循环脂联素水平，并与其胰岛素增敏作用一致。脂联素的两种受体AdipoR1和AdipoR2在许多组织中广泛表达，但其对人类胰岛素抵抗的生理意义仍有待充分阐明。我们研究了人类受试者脂肪和骨骼肌中AdipoR1和AdipoR2的表达模式，它们与胰岛素作用的关系，以及它们是否受TZDs调控。两种AdipoRs的表达模式在皮下和网膜脂肪库中相似，在脂肪细胞中的表达高于基质细胞和巨噬细胞。为了确定TZD对AdipoR表达的影响，在45 mg吡格列酮或安慰剂21天后，对14名患有2型糖尿病的胰岛素抵抗受试者的皮下脂肪和四头肌进行活检。吡格列酮的这一持续时间改善了胰岛素对葡萄糖产生的抑制41%，并增强了对葡萄糖摄取的刺激27%，同时增加了脂联素的基因表达和血浆水平。吡格列酮不影响肌肉、全脂肪或细胞脂肪组分中的AdipoR表达，受体表达与基线或TZD增强的胰岛素作用无关。总之，两种脂联素受体都在人脂肪的细胞组分中表达，特别是脂肪细胞。TZD给药足够的时间来改善胰岛素作用和增加脂联素水平并不影响AdipoR1或AdipoR2的表达。虽然TZDs可能通过脂联素发挥其许多作用，但这些受体的变化似乎不是其胰岛素增敏作用所必需的。
Circulating adiponectin levels are increased by the thiazolidinedione (TZD) class of PPAR gamma agonists in concert with their insulin-sensitizing effects. Two receptors for adiponectin (AdipoR1 and AdipoR2) are widely expressed in many tissues, but their physiological significance to human insulin resistance remains to be fully elucidated. We examined the expression patterns of AdipoR1 and AdipoR2 in fat and skeletal muscle of human subjects, their relationship to insulin action, and whether they are regulated by TZDs. Expression patterns of both AdipoRs were similar in subcutaneous and omental fat depots, with higher expression in adipocytes than in stromal cells and macrophages. To determine the effects of TZDs on AdipoR expression, subcutaneous fat and quadriceps muscle were biopsied in 14 insulin-resistant subjects with type 2 diabetes mellitus after 45 mg pioglitazone or placebo for 21 days. This duration of pioglitazone improved insulin's suppression of glucose production by 41% and enhanced stimulation of glucose uptake by 27% in concert with increased gene expression and plasma levels of adiponectin. Pioglitazone did not affect AdipoR expression in muscle, whole fat, or cellular adipose fractions, and receptor expression did not correlate with baseline or TZD-enhanced insulin action. In summary, both adiponectin receptors are expressed in cellular fractions of human fat, particularly adipocytes. TZD administration for sufficient duration to improve insulin action and increase adiponectin levels did not affect expression of AdipoR1 or AdipoR2. Although TZDs probably exert many of their effects via adiponectin, changes in these receptors do not appear to be necessary for their insulin-sensitizing effects.