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With an end to characterize the mechanism of glucose intolerance during bile-duct obstruction, studies were carried out, as follows: 1) Clinically, patients with different liver disorders (obstructive jaundice, liver cirrhosis and chronic hepatitis) were subjected to oral glucose tolerance test (OGTT), and the responses of 30K-immunoreactive glucagon (IRG) during OGTT were studied. 2) In animal experiments using rabbits, percutaneous choledochoduodenal drainage was settled in animal models to find out the bearing of the status of bile inflow on IRG response during OGTT. Futhermore, the clearance rates of glucagon and insulin in the liver as well as the biliary levels of IRG and immunoreactive insulin (IRI) were determined in these animals.The findings are summarized, as follows: 1) All patients were hyperglucagonemic. However, the paradoxical response of IRG during OGTT could be observed in only those patients with obstructive jaundice. IRG detected in hyperglucagonemic patients with biliary stagnation was large molecular IRG. 2) In rabbits under obstruction of the common bile-duct, hyperglucagonemia and the paradoxical response of IRG during OGTT were noticed as in man. When the extracorporeal loop was opened, hypoglucagonemia was induced, but the IRG responce during OGTT was depressed. It was confirmed that the bile-duct is important metabolic pathway for glucagon and insulin, and that the biliary levels of IRG and IRI were approximately 200 times and 4 times the plasma levels, respectively.The above findings suggest that glucose intolerance during bile-duct obstruction is associated with hyperglucagonemia due to bile stasis which is characterized by high circulating levels of large molecular IRG.
- 財団法人 日本消化器病学会の論文