Akira Yanbe

Hepatic steatosis and the elevated plasma insulin level in patients with endogenous hypertriglyceridemia

Among 31 nonobese or obese patients with endogenous hypertriglyceridemia, hepatic steatosis was found by histologic examination of the biopsied specimen in 17 patients, and it was severe in six patients, They had no history of excessive alcohol intake. Chemical analysis revealed that the lipid accumulated in the liver was triglyceride. The hypertriglyceridemic patients, with or without histologic steatosis, showed significantly increased responses of both plasma insulin and blood glucose to oral glucose load compared with control subjects. The responses were more exaggerated in the hypertriglyceridemic patients with steatosis than in the hypertriglyceridemic patients without steatosis. Analysis of correlations between five variables (liver triglyceride, plasma insulin, blood glucose, body weight index, and serum triglyceride) was done on 15 subjects whose liver triglyceride values were quantified, and highly significant correlations were found between liver triglyceride and plasma insulin, blood glucose, or body weight index. A step wise multiple regression analysis performed on the five variables with liver triglyceride as the dependent variable revealed that the plasma insulin level was the most closely related variable, and the blood glucose level the next. The prediction equation for liver triglyceride as a function of plasma insulin and blood glucose levels (r = 0.91, p greater than 0.001) accounted for 84 percent of the total variance of liver triglyceride. It was shown that the decay of intravenously injected insulin in plasma was not delayed in the hypertriglyceridemic patients with steatosis, while the insulin sensitivity examined after intravenous insulin injection significantly decreased in the hypertriglyceridemic patients with or without steatosis, thus suggesting that the hyperinsulinemia in the hypertriglyceridemic patients was due to an increased insulin secretion associated with the decrease in the insulin sensitivity. Therefore, the elevated plasma insulin and blood glucose levels--or the insulin insensitivity by itself--might be the essential abnormalities in patients with endogenous hypertriglyceridemia, which, in extreme cases, might lead to massive triglyceride accumulation in the liver.

CHARACTERIZATION OF CIRCULATING IMMUNOREACTIVE GLUCAGON IN RESPONSE TO INTRADUODENAL ADMINISTRATION OF FAT IN DOGS

Experimental studies were carried out to characterize the total immunoreactive glucagon (IRG) of plasma in response to the intraduodenal administration of fat in dogs. When butter or corn oil, in a dose of 2 g per kg of body weight, was administered into the duodenum of conscious dogs, total IRG in the vena cava increased significantly from the fasting level. In the experiment using conscious dogs with triple catheters, the rise in total IRG of plasma after fat loading was observed to consist of an early increase of total IRG in the pancreatic vein and a later rise of total IRG in the mesenteric vein. The rise in total IRG of plasma after fat loading continued after the removal of the pancreas. When butter was administered into the distal ileum of conscious dogs, total IRG in the vena cava increased for 2 hr, whereas pancreatic glucagon remained unchanged. The direct infusion of chyle into the pancreatic artery failed to induce an increase in total IRG in the pancreatic vein. From this experiment it was concluded that the increase in circulating total IRG after fat loading derives from gut glucagon-like immunoreactivity and from pancreatic glucagon. This study also suggests that the secretion of pancreatic glucagon is mediated through enteric signals, probably pancreozymin.

Plasma glucagon in insulinoma.

SummaryNine patients with insulinoma were studied in order to investigate glucagon levels in the fasting state and the response of plasma glucagon to tolbutamide and arginine. Fasting plasma glucagon levels were within the normal range in all patients except two cases with malignant insulinoma. Although there was no correlation between blood glucose and plasma glucagon, a significant correlation between plasma glucagon and plasma insulin was observed. No detectable changes were found in glucagon levels during tolbutamide injection. In almost all patients except one an exaggerated response of plasma glucagon was demonstrated during arginine infusion test.