| Project/Area Number |
15500318
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Kumamoto University |
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Principal Investigator |
NISHIDA Kenro Kumamoto University, University Hospital, Research Associate, 医学部附属病院, 助手 (50336244)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Eiichi Kumamoto University, Faculty of Medical and Phamaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (10253733)
SAKAKIDA Michiharu Kumamoto University, Faculty of Medical and Phamaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (50170577)
NISHIKAWA Takeshi Kumamoto University, Faculty of Medical and Phamaceutical Sciences, Research Associate, 大学院・医学薬学研究部, 助手 (70336212)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Artificial endocrine pancreas / Intraportal insulin infusion / Closed-loop insulin infusion algorithm / Compartment model / Hepatic glucose uptake / net hepatic glucose balance |
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| Research Abstract |
To establish the ideal insulin delivery route for an artificial endocrine pancreas, we examined the significance of closed-loop portal insulin delivery. We investigated the effects of route of insulin delivery on net hepatic glucose balance(NHGB) in dogs under a pancreatic clamp (somatostatin plus basal glucagon and insulin infusions). A constant rate of suprabasal insulin was infused via the portal vein or a peripheral vein, and glucose was infused into the portal vein for 180 min. The mean net hepatic glucose uptake(NHGU) values in the portal insulin infusion group(PI group) were significantly greaterthan those in the peripheral venous insulin infusion group(VI group)(change from baseline at 180 min;3.54±0.66 and 2.45±0.82 mg・kg^<-1>・min^<-1> in the PI and VI group, respectively, P<0.05). Furthermore, dogs under apancreatic clamp were controlled after a 2 g/kg oral glucose load by applying the closed-loop intraportal(PO) or intravenous(IV) insulin infusion algorithm. There were no significant differences in glycemic control and insulin requirement between these algorithms. However, the maximum peripheral venous and arterial plasma insulin concentrations with the PO algorithm were significantly lowerthan those with the IV algorithm(56.9±11.5 and 78.0±11.1 μU/ml[peripheral vein],50.9±10.5 and 78.3±14.2 μU/ml[artery], with the PO and IV algorithms, respectively,P<0.05). On the other hand, the maximum portal plasma insulin concentration with the PO algorithm was significantly higher than that with the IV algorithm(103.3±16.9 and 69.1±13.3 μU/ml, with the PO and IV algorithms, respectively,P<0.05). The mean NHGU values with the PO algorithm were significantly greater than those with the IV algorithm. Our results confirmed that the closed-loop portal insulin delivery is feasible with regard to both insulin profiles and hepatic glucose handling in vivo, and indicated that the portal vein is the most ideal insulin delivery route for the AEP.
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