Eivind Grong1, Bård Kulseng2,3, Ingerid Brænne Arbo4, Christoffer Nord5, Maria Eriksson5, Ulf Ahlgren5, Ronald Mårvik2,3,6. 1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), PB 8905, 7491, Trondheim, Norway. eivig@stud.ntnu.no. 2. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), PB 8905, 7491, Trondheim, Norway. 3. Centre of Obesity, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 4. Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 5. Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden. 6. Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Abstract
BACKGROUND: In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans. METHODS: Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining. RESULTS: Body weight did not differ between groups (P(g) = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (P(g) = 0.037); HbA1c levels in SG were lower compared to DJ only (p < 0.05). GLP-1 levels were elevated for DJ compared to SG and sham (P(g) = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (P(g) = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036). CONCLUSION: Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.
BACKGROUND: In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans. METHODS: Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining. RESULTS: Body weight did not differ between groups (P(g) = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (P(g) = 0.037); HbA1c levels in SG were lower compared to DJ only (p < 0.05). GLP-1 levels were elevated for DJ compared to SG and sham (P(g) = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (P(g) = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036). CONCLUSION: Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.
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