E Grong1,2, C Nord3, I B Arbo4, M Eriksson3, B E Kulseng4,5,6, U Ahlgren3, R Mårvik4,5,7. 1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway. eivind.grong@ntnu.no. 2. Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. eivind.grong@ntnu.no. 3. Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden. 4. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway. 5. Centre for Obesity Research and Innovation (ObeCe), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 6. Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 7. Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 6 weeks 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 18 weeks (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). CONCLUSIONS: 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 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.
PURPOSE: 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. METHODS: 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. RESULTS: 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 6 weeks 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 18 weeks (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). CONCLUSIONS: 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 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.
Authors: S Sanduleanu; M Stridsberg; D Jonkers; W Hameeteman; I Biemond; G Lundqvist; C Lamers; R W Stockbrügger Journal: Aliment Pharmacol Ther Date: 1999-02 Impact factor: 8.171