Molecular mechanisms of diabetes reversibility after bariatric surgery.
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.


METHODS
Eight Caucasian obese diabetic patients (BMI 52.1+/-1.85 kg/m(2)) were studied before and 3 years after BPD.


METHODS
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 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.


CONCLUSIONS
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.
Rosa
G
G
Department of Internal Medicine, Catholic University S Cuore, Rome, Italy. giuseppina.rosa@rm.unicatt.it
Mingrone
G
G
Manco
M
M
Euthine
V
V
Gniuli
D
D
Calvani
R
R
Calvani
M
M
Favuzzi
A M R
AM
Castagneto
M
M
Vidal
H
H
D050110:Bariatric Surgery; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009767:Obesity, Morbid / Q000378:metabolism / Q000601:surgery*; D011184:Postoperative Period; D015431:Weight Loss
D001786:Blood Glucose; D007328:Insulin