Endocrine Abstracts

Somatostatin is a hormone and neuropeptide expressed in the pancreas, gastrointestinal tract, hypothalamus, and other tissues. It regulates directly the secretion of insulin, glucagon, many of the gastrointestinal hormones, and growth hormone. It is therefore surprising the somatostatin knockout (sst-ko) mice have a very mild phenotype. We subjected sst-ko mice and heterozygous siblings which served as controls to a high-calorie diet, and confirmed that sst-ko mice gain weight normally and have slightly more adipose tissue. Continuous glucose measurement of these mice has shown they have lower glycemia than controls. both groups of mice lost weight and regained weight at the same rate after a short transition to a normal chow diet. However, sst-ko mice did not regain weight following sleeve gastrectomy (SG), a common bariatric surgery. Sst-ko mice maintained low weight 90 days after surgery, while fed on a high-calorie diet and were leaner than heterozygous siblings that had the same procedure. SG operated sst-ko mice had low fasting insulin levels, and very rapid glucose clearance. Mechanistically, SG sst-ko mice had an exaggerated post-prandial Glp1 secretion. Post-prandial Glp1 levels were higher than in heterozygous controls that had the same surgery. Sham-operated sst-ko mice did not display an elevation in Glp1 secretion. In conclusion, by performing sleeve gastrectomy on sst-ko mice we were able to expose a role for somatostatin in regulation glycemia and weight gain, in part via regulating postprandial Glp1 secretion.