Human growth hormone (HGH), FFA, I RI and blood glucose were determined during the intravenous infusion of arginine, nicotinic acid and glucose in diabetic, borderline and non-diabetic subecjts. 1. Single 1-arginine infusion (0.4g/kg) caused no change of HGH levels in 12 diabetic subjects. 2. Because of low response of HGH after single dose in diabetics, double arginine infusions (0.3g/kg at zero time and at 90 minutes) were given. 20 diabetic subjects showed slight change of HGH levels and the peak response of HGH was observed at 60 minutes after the start of the second infusion. 3. Maximum HGH value/basal HGH value after double arginine infusions was significatly smaller in diabetic subjects. 4. In 9 diabetic subjects, intravenous administration of nicotinic acid (100 mg x 2) caused no increase of HGH levels and significant decrease of the secondary rise of FFA. 5. Among 10 diabetic subjects who had glucose (0.5 g/kg) infusion for 3 minutes, 5 subjects showed marked rise of HGH levels. 6. HGH responses to double arginine infusions, nicotinic acid and glucose in borderline subjects were similar to the diabetic response pattern. 7. The first arginine infusion caused marked increase of HGH levels, but HGH response to the second arginine infusion was markedly reduced in 7 non-diabetic subjects. These results of diabetics suggest some implication of the abnormality of HGH secretion in these states.
A method for the determination of free, active insulin in the sera of the insulin-treated diabetics by radioimmunoassay with previous precipitation of anti-insulin antibody by polyethylene glycol treatment was described. The recovery test with cold insulin showed eighty-nine per cent of recovery of free insulin and no recovery of antibody-bound insulin. The fasting free insulin levels of the patients were slightly lower as compared to that of normal persons except some patients with infections and liver diseases and showed no correlation to the antibody titer, total insulin levels, insulin requirement and term of insulin treatment. The negligible increase of free insulin levels was observed in the course of glucose tolerance test of the insulin-treated patients but a marled increase of free insulin followed by a exaggerated increase of the total insulin was observed in a patients with insulin autoimmune syndrome. The diurnal changes of free insulin suggested us the usefulness of the determination of free insulin level for the control of diabetes with insulin treatment.
The insulin binding substance and serum insulin observed in a newborn infant and her mother not previously treated with insulin, were studied with immunological methods. The insulin binding substance in those patients showed quite similar characteristics to that of insulin treated patients in sephadex chromatography, agarose electrophoresis and radioimmunoelectrophoresis. However, further studies showed that the substance was pure IgG antibody with K-chain as light chain and stronger affinity to human and porcine insulin as compared to bovine insulin in contrast to the antibody of the insulin treated patients. The peripheral lymphocytes of the mother produced anti-insulin antibody in in vitro tissue culture. The serum insulin of the patients showed no detectable abnormality with dilution test and insulin degradation test with insulin specific peptidase. It is concluded that the insulin binding substance in those patients is a insulin antibody produced not by exogenous insulin but probably against endogenous insulin by denaturation of endogenous insulin or changes of antibody producing mechanism.
One hundred and eighty three diabetic death cases were collected from 11 clinics in Fukuoka prefecture over the 5 year period 1966-1970. In this study 97 cases were autopsied. The causes of death among 136 primary diabetes were as follows; vascular complications accounted for cause of death in 67 cases, in which diabetic renal lesion (24 cases) was the most frequent cause and was followed by cerebrovascular (23 cases), cardiovascular diseases (19 cases) and the other (1 case). Malignant tumors accounted for cause of death in 44 cases. In this group cancer of the stomach (12 cases) was frequent tumor as seen in general population, and next cause was cancer of the pancreas (6 cases). Infection accounted for cause of death in 7 cases, mostly urinary tract infection. Diabetic coma accounted for in 6 cases and hypoglycemia in 3 patients. In this study 47 cases were classified as the secondary diabetes including cirrhosis of liver (24 cases), cancer of the pancreas (9 cases), cancer of the liver with cirrhosis (5 cases), and the others (9 cases). The outstanding differences between the data reported by Dr. Yoshida in 1961 and the present result are the increment in vascular complications and malignant diseases and the decline in diabetic coma and infection. It is clear that the longevity of the diabetics has increased vascular and malignant diseases and recent advances of the diabetes treatment have decreased the diabetic coma and the purulent disease.
Intravenous administration of maltose (0.4g/kg) in anesthetized dogs produced acute and marked increases in plasma glucose and insulin concentrations to nearly the same extents as the increases after intravenous administration of an equivalent dose of glucose. Plasma maltose disappeared immediately after the injection of maltose. In contrast, intravenous administration of maltose (0.5g/kg) in unanesthetized rabbits failed to produce any significant rises in plasma glucose or insulin concentrations, although plasma maltose concentration increased markedly after maltose injection. This species difference may be ascribed to the difference of plasma maltase activity between these two animals. According to previous reports, maltose is well metabolized in rabbits despite the low plasma maltase activity. The implications of these findings with glucoseinduced insulin secretion are discussed.