The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats.

Abstract

Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals. Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole+sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle+sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography. After surgery, body weight development was equal among groups (P g=0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p<0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p<0.05 and p=0.052). HbA1c was lower for GK-SG vs. GK-V at 6weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p<0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18weeks (p=0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p<0.05 for all). Beta-cell mass did not differ among groups (p=0.35). Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.