Biomedical subjects
Publications and source records attributed to S Kadowaki.
Fasting plasma gastrin levels measured by radoimmunoassay were found to be low in patients with hypothyroidism. The intravenous infection of arginine caused an increase of plasma gastrin in hypothyroid patients but was significantly lower than those in normal subjects. The decreased gastrin level in patients with hypothyroidism was significantly improved after the thyroid function was normalized by treatment.
Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.
Plasma glucagon levels were determined after 50 g of oral glucose loading in eleven acromegalics and fourteen normal subjects. Basal plasma glucagon levels were significantly elevated in patients with acromegaly, as compared with those in normal subjects. Oral glucose loading caused a decrease in plasma glucagon in normal subjects but not in acromegalics. Since this non-suppressibility of plasma glucagon by orally administered glucose was observed even in acromegalics without diabetes, it is concluded that insensitivity of the pancreatic alpha cell to hyperglycaemia exists in patients with acromegaly as well as in diabetics.
The acute in vitro effect of alloxan on glucagon and insulin secretion from the isolated perfused rat pancreas was examined. Alloxan alone produced transient insulin secretion. Pretreatment with alloxan attenuated both the stimulatory effect of glucose on insulin secretion and the inhibitory effect of glucose on glucagon secretion. Exposure to alloxan in varying doses either partially or completely inhibited insulin secretion induced by arginine in the presence or absence of glucose. On the contrary, pretreatment with alloxan produced complex effects on arginine-induced glucagon secretion. In the absence of glucose, the response of glucagon to arginine infusion was lower in the pancreas exposed to alloxan than in the control experiment. In the presence of glucose, however, an apparently augmented response of glucagon to arginine was observed after exposure to higher doses of alloxan, suggesting an impaired inhibitory effect of glucose on arginine-induced glucagon secretion. These effects of pretreatment with alloxan on glucagon secretion can not be explained by earlier or simultaneous insulin secretion. Therefore, we conclude that alloxan acts not only on beta-cells, but also directly on alpha-cells, although the latter are less sensitive to this agent.
Plasma glucagon response to glucose in diabetic subjects was observed before and after treatment. In normal subjects, plasma glucagon concentrations decreased substantially after an oral glucose load. In all diabetic patients before treatment, plasma glucagon was not suppressed and rather tended to rise paradoxically despite pronounced hyperglycemia. In diabetics treated with sulfonylurea or insulin, basal plasma glucagon concentrations were significantly lower than those in patients who were not treated. However, plasma glucagon response to an oral glucose load was not normalized by successful treatment with sulfonylurea or insulin, in spite of improvement of glucose tolerance. These results suggest that the insensitivity of the A-cell to hyperglycemia exists after treatment, and this abnormal plasma glucagon response to glucose after treatment may be caused either by impaired response of endogenous insulin to glucose, which is sustained even after treatment, or by an intrinsic defect of the A-cell.
Effect of synthetic gastric inhibitory polypeptide (GIP) on insulin and glucagon secretion was stuied in vivo and in vitro in the rat. Intravenous administration of 1 microng./kg. GIP along with 0.625 gm./kg. glucose caused a more prominent rise of plasma insulin than did 0.625 gm./kg. glucose alone. The suppression of plasma glucagon levels induced by glucose was attenuated partially but not significantly by the concomitant administration of GIP. GIP (1 microng./kg. i.v.) alone raised both plasma insulin and glucago levels. In in-vitro experiments with isolated pancreatic islets, GIP significantly augmented insulin release induced by either 8.3 mM or 16.7 mM glucose, whereas the augmentation of glucagon release was observed at 3.3 mM, 8.3 MM, and 16.7 mM glucose concentrations. Three peptides, consisting of 1-28, 22-43, and 15-43 amino acids of GIP, failed to potentiate insulin and glucagon secretion. These results suggest that synthetic GIP has a stimulating effect on insulin and glucagon secretion.
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The activity of free tissue plasminogen activator (f-tPA) and plasminogen activator inhibitor (PAI) in the plasma of 82 noninsulin-dependent diabetics (NIDDM) was measured by bioimmunoassay of the euglobulin fraction obtained from the plasma, and the levels were compared with those of age- and gender-matched normal subjects. Comparison of these levels in both groups revealed that the f-tPA activity tended to be lower in NIDDM than in the controls, although the differences were not significant. Normal activity of PAI was seen, but f-tPA in NIDDM, when accompanied by macroangiopathy such as ischemic heart disease, was significantly depressed. When glycosylated hemoglobin levels were in excess of 10%, the f-tPA activity was significantly decreased, but no reduction was found in PAI activity as compared with controls. When NIDDM is associated with either macroangiopathy or high glycosylated hemoglobin levels, a decreased f-tPA activity, rather than an increased PAI activity, may contribute to the development of a defective fibrinolytic state.