Perioperative glycemic control is important for reducing postoperative infectious complications. However, clinical trials have shown that efforts to maintain normoglycemia in intensive care unit patients result in dev...Perioperative glycemic control is important for reducing postoperative infectious complications. However, clinical trials have shown that efforts to maintain normoglycemia in intensive care unit patients result in deviation of glucose levels from the optimal range, and frequent attacks of hypoglycemia. Tight glycemic control is even more challenging in those undergoing pancreatic resection. Removal of lesions and surrounding normal pancreatic tissue often cause hormone deficiencies that lead to the destruction of glucose homeostasis, which is termed pancreatogenic diabetes. Pancreatogenic diabetes is characterized by the occurrence of hyperglycemia and iatrogenic severe hypoglycemia, which adversely effects patient recovery. Postoperatively, a variety of factors including surgical stress, inflammatory cytokines, sympathomimetic drug therapy, and aggressive nutritional support can also affect glycemic control. This review discusses the endocrine aspects of pancreatic resection and highlights postoperative glycemic control using a closed-loop system or artificial pancreas. In previous experiments, we have demonstrated the reliability of the artificial pancreas in dogs with total pancreatectomy, and its postoperative clinical use has been shown to be effectiveand safe, without the occurrence of hypoglycemic episodes, even in patients after total pancreatectomy. Considering the increasing requirement for tight perioperative glycemic control and the recognized risk of hypoglycemia, we propose the use of an artificial endocrine pancreas that is able to monitor continuously blood glucose concentrations with proven accuracy, and administer automatically substances to return blood glucose concentration to the optimal narrow range.展开更多
Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulati...Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a dosed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.展开更多
To pursue insulin and islet transplantation replacement therapy for type 1 diab etes based on engineered human non β cells which secrete mature insulin Methods Human proinsulin cDNA was cloned from its genomic ge...To pursue insulin and islet transplantation replacement therapy for type 1 diab etes based on engineered human non β cells which secrete mature insulin Methods Human proinsulin cDNA was cloned from its genomic gene and mutated by overlap e xtension PCR, introducing furin consensus cleavage sequences (Arg Xaa Lys/Arg Arg) An expression vector encoding a genetically modified human proinsulin c DNA was generated and transduced to Hela, 293, and L02 cells by lipofectin medi ated DNA transfection Following G418 screening, the surviving L02 cells were s elected and enriched Insulin levels in the supernatant and cells were evaluate d using radioimmunoassay and immunofluorescence staining Results Three sites in the insulin gene were mutated simultaneously Insulin gene m odified cells were able to express insulin at different levels: 8 45-188 00? μIU/24 h/2 0×10 6 Hela cells and 159 88-242 14?μIU/24 h/2 0×10 6 293 cells for transient expression, and 2 56-61 95?μIU/24 h/2 0×10 6 from se veral L02 clones screened with G418 No insulin was released by control cells Furthermore, immunofluorescence staining confirmed that proinsulin was stored a s vacuoles in the cytoplasm of L02 cells Conclusion A correctly mutated human proinsulin cDNA was obtained successfully, transfected and expressed efficiently in non beta cells, lending support to the study of s omatic gene therapy in diabetes mellitus展开更多
文摘Perioperative glycemic control is important for reducing postoperative infectious complications. However, clinical trials have shown that efforts to maintain normoglycemia in intensive care unit patients result in deviation of glucose levels from the optimal range, and frequent attacks of hypoglycemia. Tight glycemic control is even more challenging in those undergoing pancreatic resection. Removal of lesions and surrounding normal pancreatic tissue often cause hormone deficiencies that lead to the destruction of glucose homeostasis, which is termed pancreatogenic diabetes. Pancreatogenic diabetes is characterized by the occurrence of hyperglycemia and iatrogenic severe hypoglycemia, which adversely effects patient recovery. Postoperatively, a variety of factors including surgical stress, inflammatory cytokines, sympathomimetic drug therapy, and aggressive nutritional support can also affect glycemic control. This review discusses the endocrine aspects of pancreatic resection and highlights postoperative glycemic control using a closed-loop system or artificial pancreas. In previous experiments, we have demonstrated the reliability of the artificial pancreas in dogs with total pancreatectomy, and its postoperative clinical use has been shown to be effectiveand safe, without the occurrence of hypoglycemic episodes, even in patients after total pancreatectomy. Considering the increasing requirement for tight perioperative glycemic control and the recognized risk of hypoglycemia, we propose the use of an artificial endocrine pancreas that is able to monitor continuously blood glucose concentrations with proven accuracy, and administer automatically substances to return blood glucose concentration to the optimal narrow range.
文摘Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a dosed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.
基金agrantfromtheShanghaiMunicipalGovernment (No 9841190 2 4)
文摘To pursue insulin and islet transplantation replacement therapy for type 1 diab etes based on engineered human non β cells which secrete mature insulin Methods Human proinsulin cDNA was cloned from its genomic gene and mutated by overlap e xtension PCR, introducing furin consensus cleavage sequences (Arg Xaa Lys/Arg Arg) An expression vector encoding a genetically modified human proinsulin c DNA was generated and transduced to Hela, 293, and L02 cells by lipofectin medi ated DNA transfection Following G418 screening, the surviving L02 cells were s elected and enriched Insulin levels in the supernatant and cells were evaluate d using radioimmunoassay and immunofluorescence staining Results Three sites in the insulin gene were mutated simultaneously Insulin gene m odified cells were able to express insulin at different levels: 8 45-188 00? μIU/24 h/2 0×10 6 Hela cells and 159 88-242 14?μIU/24 h/2 0×10 6 293 cells for transient expression, and 2 56-61 95?μIU/24 h/2 0×10 6 from se veral L02 clones screened with G418 No insulin was released by control cells Furthermore, immunofluorescence staining confirmed that proinsulin was stored a s vacuoles in the cytoplasm of L02 cells Conclusion A correctly mutated human proinsulin cDNA was obtained successfully, transfected and expressed efficiently in non beta cells, lending support to the study of s omatic gene therapy in diabetes mellitus
