The metabolic role of Somatostatin in sleeve gastrectomy

First discovered as the inhibitor of Growth hormone, somatostatin (SST) is a neurotransmitter and a hormone expressed in the hypothalamus, enteric nervous system, stomach, intestine, colon and pancreas. SST signaling inhibits secretion of hormones, neuronal activity and exocrine function of many cell types.

Surprisingly SST knockout (SST-ko) mice display a rather normal phenotype. We challenged the SST-ko mice with a high fat high sucrose diet and found they have lower levels of liver triglycerides compared to their heterozygous. In contrast, the total fat percent was higher in the SST-ko mice, as measured by MRI. Using a continuous glucose monitor we observed that SST-ko mice have a wider variance of glucose levels and maintain lower glucose levels.

Bariatric surgery leads to weight loss, and hypersecretion of several gastrointestinal and pancreatic hormones that are normally repressed by SST. We performed sleeve gastrectomy (SG) or sham surgery on SST-ko mice and their heterozygous littermates and observed that SST-ko mice regained less weight, had lower glucose and better glucose tolerance than all other groups. Mechanistically, these mice had high fasting levels and a powerful postprandial surge of Glp-1, an intestinal hormone that stimulates insulin secretion and induces satiety.

Daily injections of a somatostatin receptor inhibitor following SG produced similar results to those we observed in SST-ko mice following SG: Inhibitor treated mice regained less weight, had lower glucose levels and higher levels of Glp-1 following combined treatment of the surgery and inhibitor.