Department of Endocrinology, Zhongnan Hospital, Wuhan University, Wuhan 430071, People's Republic of China.
J Mol Endocrinol. 2010 Mar;44(3):179-85. doi: 10.1677/JME-09-0088.
Hypoadiponectinemia and hyperresistinemia may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature. However, the mechanism that mediates the aberrant production of adipokines remains poorly understood. In this study, we have investigated the effect of intermittent high glucose on the expression of adiponectin and resistin, and the production of 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine in the adipocytes, either in the presence or in the absence of Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or thenoyltrifluoroacetone (TTFA). 3T3-L1 adipocytes were incubated for 72 h in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, 5 mmol/l alternating with 20 mmol/l glucose, with or without MnTBAP and TTFA. We measured the expression of resistin and adiponectin. The production of nitrotyrosine and 8-OHdG as oxidative stress parameter was measured. Both constant and intermittent high glucose significantly suppressed the expression and secretion of adiponectin, and increased expression and secretion of resistin in mature adipocytes compared to normal glucose conditions. However, these effects were significantly greater under intermittent high glucose conditions compared to constant high glucose. The levels of nitrotyrosine and 8-OHdG were significantly elevated under both intermittent and constant high glucose conditions, the effect being greater under intermittent high glucose. In addition, the antioxidants MnTBAP or TTFA reversed the aberrant production of adiponectin and resistin, as well as overproduction of nitrotyrosine and 8-OHdG in adipocytes induced by constant or intermittent high glucose. Intermittent high glucose exacerbates the aberrant production of adiponectin and resistin through reactive oxygen species overproduction at the mitochondrial transport chain level in adipocytes, indicating that glycemic variability has important pathological effects on the secretion of adipokines.
低脂联素血症和高抵抗素血症可能在介导脂肪细胞向胰岛素敏感组织和血管传递信号方面发挥重要作用。然而，介导脂肪细胞分泌异常的机制仍知之甚少。在这项研究中，我们研究了间歇高葡萄糖对脂肪细胞中脂联素和抵抗素表达以及 8-羟基脱氧鸟苷（8-OHdG）和硝基酪氨酸产生的影响，无论是在锰（III）四（4-苯甲酸）卟啉氯化物（MnTBAP）或三氟乙酰丙酮（TTFA）存在或不存在的情况下。将 3T3-L1 脂肪细胞在含有不同葡萄糖浓度的培养基中孵育 72 小时：5 mmol/l、20 mmol/l、5 mmol/l 与 20 mmol/l 葡萄糖交替，有或没有 MnTBAP 和 TTFA。我们测量了抵抗素和脂联素的表达。测量了作为氧化应激参数的硝基酪氨酸和 8-OHdG 的产生。与正常葡萄糖条件相比，持续和间歇高葡萄糖均显著抑制成熟脂肪细胞中脂联素的表达和分泌，并增加抵抗素的表达和分泌。然而，与持续高葡萄糖相比，间歇高葡萄糖条件下的这些作用更为显著。在间歇和持续高葡萄糖条件下，硝基酪氨酸和 8-OHdG 的水平均显著升高，间歇高葡萄糖的作用更大。此外，抗氧化剂 MnTBAP 或 TTFA 逆转了持续或间歇高葡萄糖诱导的脂肪细胞中脂联素和抵抗素的异常产生，以及硝基酪氨酸和 8-OHdG 的过度产生。间歇高葡萄糖通过脂肪细胞中线粒体转运链水平的活性氧过度产生加剧了脂联素和抵抗素的异常产生，表明血糖变异性对脂肪细胞分泌脂肪因子具有重要的病理作用。
