1287-PUB: SGK1-NDRG1 Signal Axis as a Key Marker Associated with Insulin Resistance and Impaired Incretin Profile in Subcutaneous and Omental Fat Depots among Obese Patients

Abstract

Objective: We have performed the comparative study of basal state of SGK-dependent signaling among obese patients with/without type 2 diabetes mellitus (T2DM). We have accomplished correlation analysis of glucose metabolism and incretin profile parameters against phosphorylation and expression parameters for SGK1 and its substrate NDRG1. Methods: 36 patients with long (>10 years) and morbid (BMI>35 kg/m2) obesity, 18 of which had normal glucose tolerance (NGT) and 18 had T2DM were enrolled in this study. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to evaluate the insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Biopsies from subcutaneous and omental fat depots were obtained during bariatric surgery for all patients and signaling states were analyzed by western blot. Results: Analysis of SGK signaling for subcutaneous fat has shown single significant intergroup difference: enhancing of pSGK-S422 phosphorylation in T2DM group, but also pNDRG-T346 level has tendency to accumulation in subcutaneous fat of NGT patients. Analysis of SGK signaling for omental fat has shown similar results: in this case accumulation of pNDRG-T346 in NGT patients was statistically significant. Correlation analysis has shown strong direct correlation of pNDRG-T346 level with BMI and AUC for GLP-1 and reverse correlation of pNDRG-T346 with Hb1Ac and AUC for glucagon. For pSGK-S422 we have observed opposite characters of correlations with the similar parameters of carbohydrate metabolism and incretin profile. Conclusions: In present work we have taken more patients and have shown critical relevance and general character of stress-dependent SGK1-NDRG1 signal axis as a marker of insulin resistance for different fat depots. Disclosure I. Stafeev: None. A. V. Vorotnikov: None. Y. V. Parfyonova: None. M. V. Shestakova: None. I. Sklyanik: None. E. Mamontova: None. S. Michurina: None. E. Shestakova: None. K. Yahyaev: None. A. Yurasov: None. E. Ratner: None. M. Menshikov: None. Funding Russian Science Foundation (17-15-01435)