Somatostatin is key to explaining the long-term effect of anatomical rearrangements after sleeve gastrectomy on glucose metabolism

Abstract

Abstract Background. Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries is able to treat diabetes (T2DM) better than many drugs. The mechanisms that underlie this phenomenon remains unclear. We propose that somatostatin (SST), isoforms, SST-14 and SST-28, are key to explaining the pathophysiological mechanisms behind T2DM improvement after SG. Methods. We underwent surgeries on three groups of Wistar rats -fasting (FC), surgery control (Sham), and SG groups-. We measured plasma levels of glucose, insulin, SST-14 and SS-28 at several weeks after surgery, islet somatostatin receptor (SSTR) and cell populations at short and long-term after surgery. We performed a Pasireotide (SST-28 analogue) infusion assay in another group of rats to confirm the influence of SST-28 plasma levels on the delta-cell population. Results. We found an elevation of the insulin response after surgery in SG animals but a decrease in insulin response in the long-term with a loss of beta cell mass. An increase in duodenal SST-28-producing cells in the duodenum and a loss of pancreatic SST-14-producing cells was measured after SG but not in controls. The expression of SSTR-5 in delta-cell populations from every group and the ability of the Pasireotide infusion assay to decrease the delta-cell population indicate the effect of SST-28 plasma levels on delta-cell maintenance. Conclusion. After SG begins with a compensatory response in the duodenum, the depletion of beta cell mass after losing the brake that constitutes SST-14 at the paracrine level. This process may explain the percentage of T2DM relapse after SG.