Seizo Kadowaki

Effect of Antisomatostatin γ-Globulin on Gastrin Release in Rats

In order to determine the mechanism of endogenous gastric somatostatin in the regulation of gastrin release, antisomatostatin rabbit γ-globulin was administered in vivo and in vitro in the rat. First, in rats anesthetized by chloral hydrate, intravenous injection of 1 ml antisomatostatin rabbit γ-globulin had no significant effect on plasma gastrin levels. Second, basal gastrin release from the isolated perfused rat stomach was not affected by the administration of antisomatostatin rabbit γ-globulin (1:99 and 1:1 dilutions). Third, the addition of antisomatostatin rabbit γ-globulin (1:99) to incubated rat antral mucosa, however, significantly increased the basal gastrin release. From these results, it is concluded that antral somatostatin exerts its inhibitory effect on basal gastrin release mainly not through the circulation but via paracrine pathways.

Epidermal growth factor stimulates prostaglandin E release from isolated perfused rat stomach.

Summary Effect of epidermal growth factor, a potent stimulator of growth in many tissues, on immunoreactive-prostaglandin E secretion from isolated perfused rat stomach was investigated. Both mouse and human epidermal growth factor (10 −7 M) evoked a marked increase in immunoreactive prostaglandin E secretion from the rat stomach. Since prostaglandin E is a potent inhibitor of gastric acid secretion, the present study suggests that the increase in prostaglandin E secretion from the stomach may be responsible for the antisecretory effect of epidermal growth factor on gastric acid.

Failre of suppress plasma glucagon concentrations by orally administered glucose in diabetic patients after treatment.

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.

Theophylline: Potentiation of Arginine-induced Somatostatin Release from the Isolated Rat Pancreas

Somatostatins release from the isolated rat pancreas was studied using a perfusion technique. Arginine at a concentration of 19 mM produced a biphasic increase in somatostatin release from the perfused rat pancreas. Both first and second phases of somatostatins increase are significantly higher in the presence of 1 mM theophylline than in the absence of the drug. These results indicate the possible inclusion of the adenylate cyclase-cyclic AMP system in the regulatory mechanism of rat pancreatic somatostatin secretion.

GROWTH HORMONE MODULATION OF ARGININE‐INDUCED GLUCAGON RELEASE: STUDIES OF ISOLATED GROWTH HORMONE DEFICIENCY AND ACROMEGALY

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.

ACROMEGALY: INSENSITIVITY OF THE PANCREATIC ALPHA CELL TO HYPERGLYCAEMIA

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 hyper‐glycaemia exists in patients with acromegaly as well as in diabetics.