Shoichi Yamagata

Glucagon response to arginine after treatment of diabetes mellitus.

To investigate the aminogenic glucagon response in diabetes mellitus, arginine infusion tests were carried out on twenty-four diabetic patients before and after treatment. Eleven healthy men served as a control group. Plasma glucagon was measured by radioimmunoassay using an antiserum, G21, specific for pancreatic glucagon. Out of twenty-four patients, five were treated with diet alone, eight with sulfonylurea, and eleven with insulin. In all these diabetic groups, the glucose tolerance improved after treatment for diabetes mellitus, while the insulin response to the glucose did not show any remarkable change. The fasting levels of the plasma glucagon did not differ from that of the normal subjects both before and after treatment. Hyperresponsfveness of the plasma glucagon to arginine infusion was observed in all diabetic groups, in comparison with that of the normal controls. The exaggerated response of the plasma glucagon to arginine was lowered following appropriate treatment in each diabetic group. However, as far as the changes in glucagon area during the arginine test are concerned, the aminogenic hyperresponsiveness of the plasma glucagon was reduced prominently in the diabetic group treated with sulfonylurea. The relationship between the response of glucose and plasma insulin and between glucose and glucagon to arginine was investigated, and the importance of the changes in the insulin:glucagon ratio was emphasized. Moreover, the possibility that long-term administration of a sulfonylurea may reduce an exaggerated glucagon response to arginine was discussed.

Hypoglycemia due to apparent autoantibodies to insulin. Characterization of insulin-binding protein.

A fifty-two year old female, admitted when unconscious, had a blood glucose level of 33 mg./100 ml. Glucose injection restored consciousness, and oral glucose loading revealed a diabetic curve. Hypoglycemic coma was not produced by tolbutamide. Total immunoreactive insulin extracted from fasting plasma ranged from 824 to 1,400 μU. per milliliter. Laparotomy did not reveal adenoma of the pancreas. The specimen of the pancreas contained 3.8 U. of insulin per gram and histologically showed an increase in the numbers of islets. Her plasma was proved to bind 131-I-insulin by gel filtration, paper chromatography and dextran-coated charcoal methods. The binding protein was identified to be gamma globulin upon paper electrophoresis and was absorbed by anti–human globulin rabbit serum. The gamma globulin was characterized as IgG on immunoelectrophoresis with radioautography. Protein fractions from the patients plasma, freed from insulin by gel filtration after acidification, reacted with pork, beef or human insulin, and dose response curves were depicted. With bonito insulin, however, it did not show any immunologic reaction. A positive skin anaphylaxis reaction was demonstrated in a guinea pig immunized with the patients plasma, but no precipitation reaction was observed. Since the patient had never received insulin injections, the results suggest that the insulin-binding protein contains antibodies which are produced against endogenous insulin.

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.

Secretory function of the stomach of Japanese with endoscopically normal gastric mucosa

SummaryUsing gastrin-like AOC-tetrapeptide the secretory function of the stomach of Japanese with endoscopically normal gastric mucosa was examined in a multicenter clinical study. Mean one hour secretion volume, mean maximal acidity, and mean maximal acid output were found to be 129.3 ±60.0 ml/hr, 103.7 ±32. 4 mEq/1, and 9.2 ±6.9 mEq/hr respectively. Results were analysed according to sex or age by analysis of variance and compared further with the corresponding data reported in the literature.

Diabetic treatment and the diurnal plasma triglyceride.

Abstract Thirteen diabetic inpatients were examined for diurnal blood sugar and plasma triglyceride levels before and after diabetic treatments. The diurnal blood sugar levels in juvenile diabetics were higher and the diurnal plasma triglyceride levels were lower than in other types of diabetics. The diurnal plasma triglyceride was most elevated in adult insulin insensitive diabetics. The amelioration of the diurnal triglyceride levels was produced in 7 of 9 cases whose diurnal blood sugar levels were normalized by a moderately-high carbohydrate diet with the administration of insulin or sulfonylurea. The improvement of both diurnal blood sugar and plasma triglyceride curves was usually parallel. The fasting plasma triglyceride levels was a good predictor of the diurnal triglyceride fluctuations in any phase of carbohydrate metabolism, whereas the fasting blood sugar did not reflect the diurnal change in subjects receiving insulin injection. The effects of diabetic treatment on the diurnal levels of blood sugar or plasma triglyceride were indefinite in unstable diabetics. The duration of diabetes or the presence of vascular complications did not give an influence on the rate of improvement of triglyceridemia.

Studies on severe hepatic damage induced by galactosamine

SummarySevere hepatic damage with submassive necrosis induced in rats by an intraperitoneal injection of a single dose of galactosamine hydrochloride was studied. In the severely damaged liver, the remarkable decreases of glycogen and UDPG in the damaged liver were seen. This means extreme decrease in the reserve power of glycolysis. Moreover, the activities of glucose-6-phosphatase and fructose-l, 6-diphosphatase decreased. Therefore, the glucose release from liver into the blood stream decreases and the inhibition of gluconeogenesis occurs. In the damaged liver, the decrease of UTP which is essential for the synthesis of sugar moiety of polysaccharide, was seen. Further, the activities of L-glutamine: D-fructose-6-phosphate amidotransferase and UDP N-acetylglucosamine 2’-epimerase which are two key enzymes of polysaccharide synthesizing enzyme were seen to decrease remarkably. In the damaged liver, the glycoprotein fraction decreased more strikingly than the acid mucopolysaccharide fraction. Moreover, the decrease of fructose-l,6-diphosphatase activity seems also to effect on the inhibition of polysaccharide synthesis. In these respects, in the sever hepatic damage, the synthesis of glycoprotein which is essential for liver cell seems to be inhibited.

Early detection of stomach cancer in mass survey

SummarySince Feburary 1960, mass survey for the stomach cancer has been undertaken on the population over the age of 40, using the indirect X-ray examination apparatus facilitated in the specially designed autmobile. The applicants are given 200 ml of 65% w/v barium and the fluorophotograms are taken at prone position, supine position, 45 degree ventral position in dorsoventral and right oblique position, and generally four to six films are taken for each cases. These films were examined by two different doctors and suspicious films for stomach lesions were selected for further examinations, including direct fluoroscopy, gastrocamera, gastrofiberscopy, gastric cytology and biopsy.The number of applicants amounted to 422,025 from Feburary 1960 to March 1967. During these periods, 794 cases with stomach cancer (0.19%), 5,600 cases with stomach ulcer (1.33%), 4,486 cases with duodenal ulcer (1.06%) and 547 cases with gastro-duodenal ulcer were found.Of stomach cancer, 180 cases were early stomach cancer, and the ratio of early cancer (at the annual meeting of JAPAN GASTROENTEROLOGICAL ENDOSCOPY SOCIETY in 1962 and of JAPANESE RESEARCH SOCIETY for GASTRIC CANCER in 1963, the early gastric carcinoma was defined as carcinoma of the stomach of which invasion was limited to the mucosa and submucosa) to all cases with operated stomach cancer is 27.0%.The prognosis of early stomach cancer is so excellent, that the significance of mass survey of stomach for detection of early cancer is stressed.

Secretin-like activity in duodenal mucosa and peptic ulcer

SummaryThe secretin-like activity contained in bioptic specimens of duodenal mucosa was measured by means of bioassay in healthy controls and patients of peptic ulcer. It was found that the activity tended to be increased in duodenal ulcer in comparison with gastric ulcer which did not differ from healthy controls, Possibilities of impaired release and/or increased production of secretin-like substance in duodenal ulcer were discussed.

Clinical Application of Xylitol in Diabetes

As a result of the pioneering experiments of Dr. Lang and his coworkers [1], and the subsequent clinical investigations of Prellwitz and Bassler [2], andMehnert, Summa, and Forster [3], it became apparent that the disappearance of intravenously administered xylitol was essentially the same in normal and diabetic subjects. The production of xylitol in large quantities since 1964, made it possible to explore the use of this pentitol in clinical conditions, particularly diabetes mellitus, in which animal studies suggested a possible beneficial effect.