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An Experimental Treatment of Gastric Bypass Surgery Combined with Islet Transplantation for Diabetes Mellitus in Rats

Author: ZhengYang
Tutor: WangXiMo
School: Tianjin Medical University
Course: Surgery
Keywords: Diabetes Mellitus Gastric Bypass Surgery Islet Transplantation Islet Function Rat
CLC: R587.1
Type: Master's thesis
Year: 2013
Downloads: 4
Quote: 0
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Abstract


STZ-induced diabetic Wistar rats who remained different residual islet function underwent duodenal jejunal bypass surgery surgery, and we confirmed that residual islet function determined the treatment effect of gastric bypass surgery for diabetes mellitus. Using the modified method, the islet isolated and purified from rats with different weight had stable high yield and good quality. STZ-induced diabetic rats underwent duodenal jejunal bypass surgery surgery and/or allogeneic islet transplantation under the kidney capsule, and we evaluated the treatment effect of gastric bypass surgery combined with islet transplantation for diabetes mellitus in rats and investigated the mechanisms of gastric bypass surgery combined with islet transplantation.Part I The Impact of Residual Islet Function on Treatment Effect of Gastric Bypass Surgery for Diabetes Mellitus RatsObjective:The purpose of this study was to establish the procedure of duodenal jejunal bypass surgery for STZ-induced diabetic rats with different residual islet function, and investigate the relationship between residual islet function and treatment effect of gastric bypass surgery for diabetes mellitus.Methods:Adult male Wistar rats were randomly assigned for normal control group, low dose control group, low dose DJB group, high dose control group and high dose DJB group. Diabetes in rats with different residual islet function was induced via intraperitoneal injection of STZ with different doses. Rats of low dose DJB group and high dose DJB group underwent duodenal jejunal bypass surgery surgery. Non-fasting blood glucose, OGTT, plasma C peptide and GLP-1was measured. Pancreas tissue was collected for pathologic study. Residual islet function and treatment effect of gastric bypass surgery were compared. Results:At7th day after injection of STZ, blood glucose of groups injected STZ was higher than normal control group’s (P<0.01), while plasma C peptide were lower than normal control group’s (P<0.01). Blood glucose level of high dose control group was higher than low dose control group’s (P<0.01), and plasma C peptide of high dose control group was lower than low dose control group’s (P<0.01). Oral glucose tolerance of high dose control group was worse than low dose control group’s, and islet injury in pathological section was more serious than low dose control’s. After DJB procedure, plasma GLP-1of low dose DJB group and high dose DJB group was higher than preoperative levels (P<0.01), and also higher than low dose control group’s and high dose control group’s (P<0.01). After DJB procedure, blood glucose level of high dose DJB group decreased (P<0.01), and was lower than low dose control group’s (P<0.01). After DJB procedure, Plasma C peptide of high dose DJB group increased (P<0.01), and was higher than low dose control group’s (P<0.01), and islet pathologic injury was less than low dose control group’s. There was no significant change of postoperative blood glucose (P>0.05). plasma C peptide (P>0.05) in high dose DJB group. Oral glucose tolerance of high dose DJB group was as bad as high dose control group’s. Islet pathologic injury of high dose DJB group appeared as serious as high dose control group’s.Conclusions:Residual islet function determines treatment effect of gastric bypass surgery for diabetes mellitus. Gastric bypass surgery is inefficient, when islet function was failure.Part II The Method with High Yield for Isolation and Purification of Rat IsletsObjective:The purpose of this study was to establish an effective and stabile method for isolation and purification of rat islets.Methods:Adult male SD rats were assigned for4groups by body weight. Islets were isolated and purified using modified method. Identification of purified islets was evaluated by dithizone staining. Viability of islets was assessed by fluorescence staining of aridine orange and propidium iodide. Function of purified islets was determined by glucose-stimulated insulin release test.Results:Mean yield of purified islets from one pancreas was1056±357islets. There was no significant difference among islet yields of4groups with different body weight (P>0.05) Purity of islets was more than90percent. Viability of islets was more than90percent. Simulation index was2.08±0.10.Conclusions:Using the modified method, islets isolated and purified from rats with different weight have stable high yield and good quality.Part Ⅲ The Treatment Effect of Gastric Bypass Surgery Combined with Islet Transplantation for Diabetes Mellitus in RatsObjective:The purpose of this study was to evaluate the treatment effect of gastric bypass surgery combined with allogeneic islet transplantation under kidney capsule for diabetes mellitus in rats and to investigate mechanisms of gastric bypass surgery combined with islet transplantation.Methods Adult male Wistar rats were randomly assigned for diabetes control group, simple bypass surgery group, simple transplantation group and combination treatment group. All rats were induced to be diabetic with poor residual islet function via injection of STZ. Simple bypass surgery group underwent duodenal jejunal bypass surgery surgery. Islets were isolated and purified from adult male SD rats. Simple transplantation group underwent allogeneic islet transplantation under kidney capsule. Combination treatment group underwent allogeneic islet transplantation under kidney capsule after DJB procedure. Non-fasting blood glucose, OGTT, plasma insulin and GLP-1was measured. Pancreas tissue and islet graft was collected for pathologic study. Treatment effects of different groups were compared.Results:After DJB procedure, there was no significant change of blood glucose (P>0.05), plasma insulin (P>0.05) in simple DJB group. After islet transplantation, postoperative blood glucose(P<0.01), plasma insulin(P<0.01) and oral glucose tolerance of simple transplantation group and combination treatment group was improved compared with preoperative situation. There was no change of pancreas pathologic injury of all groups. The survival time of islet grafts in combination treatment group was longer than simple transplantation group’s (P<0.01). Pathological injury of islet grafts in combination treatment group was less than simple transplantation group’s, and inflammation in implant site of combination treatment group was less than simple transplantation group’s.Conclusions:Gastric bypass surgery combined with islet transplantation is effective for diabetes mellitus in rats with poor residual islet function and extends the survival time of islet graft.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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