Lihn A S, Østergard T, Nyholm B, Pedersen S B, Richelsen B, Schmitz O
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E443-8. doi: 10.1152/ajpendo.00358.2002. Epub 2002 Oct 8.
Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced M value (4.44 vs. 6.09 mg x kg(-1) x min(-1), P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls (P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 microg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11-13%) but significantly in both groups (P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin (P < 0.05) and positively correlated with insulin sensitivity (P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.
脂联素被认为是胰岛素抵抗的重要介质。因此，我们研究了22名2型糖尿病患者的健康一级亲属（FDR）和13名匹配的对照受试者中脂联素与胰岛素敏感性之间的关联。在高胰岛素正常血糖钳夹前后进行皮下脂肪组织活检。FDR受试者存在胰岛素抵抗，M值降低表明了这一点（4.44对6.09mg·kg⁻¹·min⁻¹，P<0.05）。与对照组相比，FDR脂肪组织中脂联素mRNA表达降低45%（P<0.01），而两组血清脂联素水平相似（6.4对6.6μg/ml，无显著性差异）。胰岛素输注使两组脂联素循环水平适度降低（11 - 13%）但具有显著性（P<0.05）。在对照组中，脂联素mRNA水平与空腹胰岛素呈负相关（P<0.05），与胰岛素敏感性呈正相关（P<0.05）。相比之下，在FDR组中未发现这些关联。总之，FDR皮下脂肪组织中脂联素mRNA降低，但循环脂联素水平正常。脂联素mRNA水平在对照受试者中与胰岛素敏感性呈正相关，但在FDR中并非如此。这些发现表明FDR中脂联素基因表达失调。
