Rosa G, Mingrone G, Manco M, Euthine V, Gniuli D, Calvani R, Calvani M, Favuzzi A M R, Castagneto M, Vidal H
Department of Internal Medicine, Catholic University S Cuore, Rome, Italy.
Int J Obes (Lond). 2007 Sep;31(9):1429-36. doi: 10.1038/sj.ijo.0803630. Epub 2007 May 22.
Insulin resistance is a strong biological marker of both obesity and type 2 diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. Biliopancreatic diversion (BPD), inducing a massive lipid malabsorption, leads to a reversion of type 2 diabetes. To elucidate the mechanisms of diabetes reversibility, the expression of genes involved in glucose and free fatty acids (FFAs) metabolism was investigated in skeletal muscle biopsies from obese, type 2 diabetic subjects. Peripheral insulin sensitivity and insulin secretion was also measured.
Eight Caucasian obese diabetic patients (BMI 52.1+/-1.85 kg/m(2)) were studied before and 3 years after BPD.
The mRNA levels were estimated by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), insulin sensitivity by the euglycemic-hyperinsulinemic clamp and insulin secretion using a model describing the relationship between insulin secretion and glucose concentration.
Whole-body glucose uptake (M), normalized by fat-free mass, significantly increased in post-obese subjects (P<0.0001). Total insulin output decreased (P<0.05) in association with a significant improvement of beta-cells glucose sensitivity (P<0.05). mRNA levels of FABP3 (P<0.05), FACL (P<0.05), ACC2 (P<0.05), HKII (P<0.05) and PDK4 (P<0.05) were significantly decreased, while SREBP1c mRNA increased (P<0.05) after BPD.
Reversibility of type 2 diabetes after BPD is dependent on the improvement of skeletal muscle insulin sensitivity, mediated by changes in the expression of genes regulating glucose and fatty acid metabolism in response to nutrient availability.
胰岛素抵抗是肥胖症和2型糖尿病的一个重要生物学标志物。骨骼肌内异常的脂肪沉积已被确定为肥胖相关胰岛素抵抗的一种机制。胆胰转流术（BPD）可导致大量脂质吸收不良，进而使2型糖尿病得到逆转。为阐明糖尿病可逆性的机制，我们对肥胖的2型糖尿病患者的骨骼肌活检样本中参与葡萄糖和游离脂肪酸（FFA）代谢的基因表达进行了研究。同时还测量了外周胰岛素敏感性和胰岛素分泌情况。
八名白种人肥胖糖尿病患者（体重指数52.1±1.85kg/m²）在接受BPD手术前及术后3年接受了研究。
通过定量实时逆转录聚合酶链反应（RT-PCR）评估mRNA水平，通过正常血糖高胰岛素钳夹技术评估胰岛素敏感性，并使用描述胰岛素分泌与葡萄糖浓度关系的模型评估胰岛素分泌情况。
经去脂体重标准化后的全身葡萄糖摄取量（M）在肥胖症患者术后显著增加（P<0.0001）。总胰岛素分泌量下降（P<0.05），同时β细胞葡萄糖敏感性显著改善（P<0.05）。BPD术后，FABP3（P<0.05）、FACL（P<0.05）、ACC2（P<0.05）、HKII（P<0.05）和PDK4（P<0.05）的mRNA水平显著下降，而SREBP1c mRNA则增加（P<0.05）。
BPD术后2型糖尿病的可逆性取决于骨骼肌胰岛素敏感性的改善，这是由调节葡萄糖和脂肪酸代谢的基因表达变化介导的，这些变化与营养物质的可利用性有关。
