The enteral insulin-stimulation after pancreas transplantation in the pig

Abstract

Summary. The insulin responses to an oral glucose tolerance test (OGTT) and in intravenous glucose infusion (IVGI), designed to copy the changes in serum glucose concentrations found during OGTT, were measured in four pigs before and after heterotopic pancreatico-duodenal allotransplantation and total pancreatectomy. After transplantation and total pancreatectomy a remarkable hyperinsulinaemia occurred during OGTT and IVGI, reflected by an almost two-fold increment in the insulinogenic index after transplantation. This finding might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein. The magnitude of the enteral stimulus, i. e. the incretin effect on insulin secretion during OGTT was unchanged after transplantation, suggesting that the incretin effect is not mediated by neural influences upon the endocrine pancreas.Key words: Glucose, incretin, insulin secretion, pancreatic transplantation, pigs.Oral glucose induces an insulin response more than twice as large as that induced by intravenous glucose [1][2][3][4]. The mechanism behind this phenomenon, termed incretin [5], has received much attention, but its nature has not yet been entirely explained. The incretin effect has mainly been conceived as being of hormonal nature [6][7][8][9][10][11]. However, it might also be due to neural augmentation of the insulin response [4,[12][13][14], though until now no studies have excluded this possibility.The present study was designed to evaluate the necessity of pancreatic innervation on the incretin effect in pigs by studying the effect of heterotopic pancreatic allotransplantation on the insulin responses to oral and intravenous glucose administration. Material and MethodsEight healthy pigs of Danish Landrace weighing 29-34 kg were used in the study.The operative procedure has been described in detail previously [15]. In short, total pancreaticoduodenectomy was performed in the donor pig, with resection of an 8 cm long segment of aorta containing both the coeliac and the superior mesenteric arteries. In the recipient pigs pancreaticoduodenal transplantation was as follows: The infrarenal vena cava and the abdominal aorta were exposed for approximately 8 cm. The distal end of the donor aortic segment was anastomosed end-to-side to the abdominal aorta of the recipient and the donor portal vein joined end-to-side to the inferior vena cava of the recipient. The duodenal segment was anastomosed end-to-side to the upper part of jejtmum. Total Pan7 createctomy was performed in the recipient pig one week after transplantation. Penicillin was given during the first postoperative week. Immunosuppressive therapy was not given.The mean survival time of the four pigs was 73.5 days (range 35-98 days). They remained normoglycaemic for an average of 63.3 days (range 21-91 days). During the investigative period all pigs were in good clinical condition without any signs of malabsorptive disorders. After death the pigs were autopsied and, to insure that there were no remaining pa...

Preserved incretin effect after complete surgical denervation of the pancreas in young pigs

“…glucose) were in the same range of approximately 55%, independent of whether the innervation of the pancreas was intact or not. This is in line with results of Lindkaer Jensen et al [11], who, however, used a different operation technique leading to systemic delivery of insulin after anastomosing the (pancreas) donor portal vein to the recipient Vena cava. This resulted in pathologic glucose tolerance and peripheral hyperinsulinemia and thus compromised the comparability of preoperative and postoperative metabolic data.…”

“…Still, the possibility remains that in the dog the contribution of nerves to the action of the enteroinsular axis is more important than in pigs. In our study and in the papers of Lindkaer Jensen et al [11] and Jakob et al [7], only the effect of pancreatic denervation on the intestinal phase of insulin secretion has been investigated (i.g. glucose instillation circumvents the stimulation of the afferent nerves of the cephalic reflex arch), while in the case of glucose ingestion the cephalic phase comes into action.…”

Insulin Secretion and Incretin Hormone Concentration in Women with Previous Gestational Diabetes Mellitus

“…Total cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol were measured using an automatic analyzer (Hitachi 747; Hitachi, Tokyo, Japan). Insulin secretion capacity was evaluated using the HOMA-beta and insulinogenic index (30 minutes) [14,15]. The SPSS program version 15.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis, and the results were expressed as mean±standard deviation.…”

Gastric Inhibitory Polypeptide and Insulin Release in Response to Oral and Intravenous Glucose in Coeliac Disease

“…The insulinogenic index was calculated as the integrated incremental insulin area divided by the integrated incremental glucose area. The incretin effect was calculated as (integrated incremental insulin area during O G T T minus integrated incremental insulin area during IVGI) divided by integrated incremental insulin area during IVGI (7).…”

“…The insulinogenic index during OGTT was 17.0 (14.9-25.0) in the patients and 10.3 (9.0-12.8) in the controls, which was a non-significant difference. During IVGI the insulinogenic indices were 5.1 (2.2-7.4) and 3.8 (1.8-5.3), respectively.The incretin effect in the patients was normal-1 7. (1.4-3.4) (in the controls, 2.0 (1.…”