Molecular and cellular mechanisms underlying reversal of type 2 diabetes following bariatric surgery: Study using proteomic and genes chip analysis

Project Summary:

Background: Obesity and type-2 diabetes (T2D) are two components of a worldwide pandemic including Saudi Arabia. Lifestyle modifications (diet/exercise) together with medications are pivotal to manage obesity and diabete. Besides, weight-loss bariatric surgery has induced T2D reversal with improved morbidity and mortality; however, the underlying mechanisms of glycemic control and T2D reversal remain unclear. Therefore, we propose to study the cellular and molecular mechanisms through which bariatric surgery restores metabolic homeostasis, insulin sensitivity and beta-cells function including signaling networks of glucose/lipid metabolism.

Methodology: For this purpose, forty adult morbidly-obese female volunteers with T2D (≥18 years; BMI ≥35Kg/m2) and scheduled for bariatric surgery will be enrolled. Blood samples will be collected at 5 time-points: preoperative/baseline, just before surgery and at 2-, 6- and 12-months postoperatively. Subcutaneous abdominal fat will be collected at surgery and 12-months postopeartively. Genomic and proteomic profiling using Affymetrix human genome GeneChip® U133-Plus2.0 array and high-resolution two-dimensional differential in-gel electrophoresis (2D-DIGE), respectively will be used to characterize the differential gene/protein expression profiles in plasma, leucocytes and adipocytes pre-and post-surgery and between the patients with or without T2D reversal. A biologically meaningful change, up-/down-regulated genes/proteins, will be considered statistically significant at ≥2-fold difference in genes/proteins expression. The results will be confirmed by RT-PCR/Western blot for one up-regulated and one down-regulated sequence or proteins spots.

Conclusions/Significance: The findings will help identify novel therapeutic targets for intervention