Molecular mechanisms of diabetes reversibility after bariatric surgery

作者：Rosa G^*; Mingrone G; Manco M; Euthine V; Gniuli D; Calvani R; Calvani M; Favuzzi A M R; Castagneto M; Vidal H

来源：International Journal of Obesity, 2007, 31(9): 1429-1436.

DOI：10.1038/sj.ijo.0803630

• type 2 diabetes
• morbid obesity
• insulin resistance
• biliopancreatic diversion
• gene expression

Objective: 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.
Subjects: Eight Caucasian obese diabetic patients (BMI 52.1 +/- 1.85 kg/m(2)) were studied before and 3 years after BPD.
Measurements: 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.
Results: 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 b-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.
Conclusion: 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.

• 出版日期2007-9