人工膵島システム開発のためのCounterregulatory System:ブドウ糖およびグルカゴン注入アルゴリズムの作成
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概要
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To accomplish an artificial endocrine pancreas system by adding a glucose and glucagon infusion mechanism in the artificial beta cell developed originally in the First Department of Medicine, Osaka University Medical School, glucose and glucagon infusion algorithms were invented.<BR>The principle of glucose or glucagon infusion algorithm is determined as the proportional plus derivative modes of action to blood glucose concentration with a time delay constant, as follows : <BR>GIR (t) = Cp [BGp - BG (t-<I>T</I>)] + Cd [-_??_BG (t-<I>T</I>)]<BR>GnIR (t) = Gp [BGp - BG (t-<I>T</I>)] + Gd [-ABG (t-<I>T</I>)] + Gc where GIR (t) and GnIR (t) are the glucose infusion rate (mg·kg<SUP>-1</SUP>min 1) and glucagon infusion rate (ng.kg<SUP>-1</SUP>.min<SUP>-1</SUP>), respectively. BGp is the projected value of blood glucose concentration (mg/100ml), and BG (t) and _??_BG (t) are blood glucose concentration at time t (mg/ 100ml) and the rate of change in blood glucose concentration at time t (mg·100ml<SUP>-1</SUP>), respectively. Cp and Cd are coefficients for glucose infusion, and Gp and Gd are those for glucagon infusion. Gc is the constant for basal glucagon infusion supplementation. <I>T</I> (min) is the time delay constant for glucose and glucagon infusion.<BR>The validation of these algorithms were attempted in depancreatized dogs. In dogs, hypoglycemias were induced by iv bolus insulin injections, then a counterregulatory system was operated according to each of these algorithms.<BR>The following results were obtained : <BR>1) When glucose was infused on the basis of the proportional action with a 20-min time delay (Cp/Cd/<I>T</I> = 0.2/0/20), the insulin-induced hypoglycemia in depancreatized dogs could be restored to normoglycemia in the same manner as seen in normal dogs.<BR>2) A speedier and less fluctuating restoration to normoglycemia could be obtained when the glucose was infused on the basis of a proportional plus derivative mode of action with a 4-min time delay (Cp/Cd/<I>T</I> = 0.5/0.5/4).<BR>3) In glucagon infusion algorithm, with the optimal parameters based on proportional plus derivative modes of action with a 10-min time delay (Gp/Gd/Gc/<I>T</I> = 0.2/0.4/0.4/10), both the blood glucose response curves and plasma glucagon profiles simulated perfectly those seen in normal dogs.<BR>4) When glucagon was infused on the basis of proportional plus derivative modes of action without the time delay (Gp/Gd/Gc/<I>T</I> = 0.5/0.5/0.4/0), hypoglycemias rarely occurred in spite of iv insulin injections with the least glucagon infusion amount.<BR>These results clearly indicate that an artificial endocrine pancreas system characterized with glucose or glucagon infusion algorithm constitutes a clinically useful device not only as a safety control against hypoglycemia, but it also enables adaptive and optimal glycemic controls. In addition, by applying these algorithms, an artificial endocrine pancreas system becomes a powerful research tool for such investigations as the dynamic property of the pancreatic a cell in glucagon secretion against blood glucose, the analysis of the effects of hormones on the glucoregulatory system and for the glucose clamp method.
- 日本内分泌学会の論文