| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Kenro Kumamoto University, Department of Medicine, Investigator, 医学部附属病院, 助手 (50336244)
ARAKI Eiichi Kumamoto University, Department of Medicine, Professor, 大学院・医学薬学研究部, 教授 (10253733)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
The ultimate goal of the development of an artificial endocrine pancreas is to achieve a long-term strict glycemic regulation. In order to establish the physiological insulin delivery route of the artificial endocrine pancreas, intraperitoneal insulin infusion may be important. For this purpose, we tried to develop closed-loop intraperitoneal insulin infusion algorithm by analyzing the pharmacokinetics of intraperitoneal regular insulin absorption using a mathematical model. The parameters for this algorithm were calculated to simulate the plasma insulin profile after intraperitoneal insulin injection as closely as possible. To evaluate the appropriateness of this algorithm, we tried glycemic control after 2-g/kg oral glucose load or 80-kcal/kg meal load in diabetic dogs by applying the algorithm. Using the subcutaneous insulin lispro infusion algorithm, which we have previously reported, alloxan-induced diabetic dogs exhibited postprandial hyperglycemia and delayed hyperinsulinemia, f
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ollowed by hypoglycemia after 2-g/kg oral glucose load. However, using the intraperitoneal insulin infusion algorithm, excellent glycemic control (postprandial blood glucose of 9.1 ± 0.8 mmol/l at 70 min and 3.8 ± 0.3 mmol/l at 240 min, respectively) could be achieved without any associated delayed hyperinsulinemia or hypoglycemia. Glycemic excursion after 80-kcal/kg meal load was also controlled from 3.9 to 10.1 mmol/l. In addition, using the IP algorithm described n this study, excellent glycemic control after either an oral glucose load in the supine position or a meal load in the standing position could be achieved in diabetic dogs. It was not necessary to change the insulin infusion parameters in response to a positional change of the dogs.
Our results confirm the feasibility of the intraperitoneal insulin infusion algorithm in vivo and that this algorithm can be superior to the subcutaneous insulin lispro infusion algorithm in the regulation of blood glucose.
In conclusion, we developed the IP algorithm, designed for the AEP, as the summation of proportional and derivative actions in response to blood glucose concentration. With the AEP operated by this algorithm, blood glucose and insulin profiles during oral glucose load and meal load were successfully regulated in diabetic dogs. These data suggest the feasibility of glycemic control with closed-loop intraperitoneal insulin infusion in the treatment of human diabetes patients. Our results might encourage the development of the implantable AEP in the near future, which could provide optimal glycemic control of patients, especially those with type 1 diabetes. Less
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