In order to clarify the nature of the biological action of gut glucagon-like immunoreactivity (GLI), GLI was extracted from the mucosa of the canine intestine and purified by gel filtration and affinity chromatography. 1500 gm of the mucosa yielded approximately 7 gm of crude extract of GLI. This crude extract was applied to a column packed with Sephadex G-50 or Bio-Gel P-10 and two peaks were obtained, Peak I and II. Each peak was purified with affinity chromatography, bound to gamma-globulin of anti-glucagon rabbit-serum. In this step, the GLI was purified approximately 80 times in comparison with the crude extract. Peak I or Peak II, as well as pancreatic glucagon, was infused successively into the pancreaticoduodenal artery of the anesthetized dogs. When buffer solution or the Peak I GLI was infused, the plasma immunoreactive insulin in the pancreatic vein did not change significantly. In contrast, both the Peak II and pancreatic glucagon promoted insulin secretion from the pancreas. The results obtained in this experiment demonstrate the promotion of insulin release from the pancreas and suggest an important role of gut GLI in the absorption and metabolic processing of nutrients.
To investigate the effect of long-term administration of oral hypoglycemic agents upon the development of vascular complications, a retrospective follow-up study was carried out on 214 diabetic patients for a period of 8 years. These patients were divided into three groups: 38 patients treated with diet alone (group I), 125 patients with sulfonylurea (group II) and 51 patients with insulin (group III). The mean fasting blood glucose levels were generally well controlled through the period of observation in each group. Blood pressure had been treated, but hypertension was observed in 2 to 10% of each diabetic group at the eighth year. Hypoglycemia, albuminuria and ketonuria occurred more frequently in group III than in the other groups. There had been no remarkable changes in serum lipids of these three diabetic groups through the observation period. The percentages of the patients with diabetic retinopathy increased during the follow-up period and significant differences were noted among the three groups at the eighth year (p<0.025). In contrast, no significant difference was demonstrated in the percentage of the ischemic heart disease among these groups. When correlation coefficients between variables in each group were calculated, it was difficult to find out any definite relationship between certain variables. The stepwise multiple-regression analyses suggested that the development of retino pathy or of abnormal ECG was affected by various factors. In addition, statisti cal analyses were performed on 152 deaths among 2100 diabetics who attended our Clinic between January 1, 1961 and August 31, 1976. The mortalities were 8.9% for the group with diet alone, 3.5% for the group with sulfonylureas and 11.9% for the group with insulin, and these values were different with a statistical significance (p<0.001). As a whole, 32 patients (21.7%) died of malignant neoplasma, 25 (16.4%) of renal diseases and 24 (15.8%) of cerebral vascular accidents. Fatal myocardial infarction and cardiac insufficiency were detected in 6 (3.9%) and 5 (3.3%) patients, respectively. The percentages of deaths from heart disease were low and no significant difference was observed in the mortality of cardiac events between the three groups. The results obtained in
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