Kozaburo Mori

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.

The failure of truncal vagotomy to affect motilin release in dogs

To elucidate the relationship between vagus nerve and motilin release, we have studied the influence of truncal vagotomy with pyloroplasty (TV) on motilin release in the fasting state and for 120 min following an intraduodenal administration of 10 g glucose in a 50-ml water solution or 5 g soybean oil. TV did not influence the intermittent fluctuation or concentration of plasma motilin in the fasting state. Intraduodenal glucose administration inhibited motilin release, but this was not affected by TV. Intraduodenal fat administration accelerated motilin release, but this effect also was not affected by TV. These results suggest that motilin secretion in the fasting state and after nutrient ingestion is not influenced by TV.

ABNORMAL PANCREATIC POLYPEPTIDE RESPONSE TO ORAL GLUCOSE LOADING IN DIABETES MELLITUS

In order to elucidate the abnormality of pancreatic polypeptide (PP) secretion in diabetes mellitus, basal plasma PP levels and their response to oral glucose loading were measured in normal subjects and diabetic patients. Fasting plasma PP levels were significantly elevated in patients with diabetes mellitus. Oral administration of 50g of glucose elicited an exaggerated rise in plasma PP in diabetic patients as compared with the response in normal subjects. This exaggerated PP response to oral glucose loading was partially but significantly improved after the treatment, with an augmented response of plasma insulin. These results indicate the existence of abnormal PP secretion in diabetes mellitus which is possibly caused by metabolic or endocrine derangements.

Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs

to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes.

Role of the duodenum in motilin release

In order to study the regulatory mechanism of motilin release, plasma motilin was measured in healthy dogs during the fasting state and after the ingestion of ordinary nutrient. Fasting plasma motilin levels were found to fluctuate intermittently, but ingestion of a meal completely abolished the intermittent motilin release and resulted in low motilin levels lasting for 6-8 h. To clarify the role of the duodenum in this motilin release, an operation was performed in five dogs by which we excluded from the alimentary tract the upper half of the small intestine not including the duodenum from a point 2 cm below the larger pancreatic duct. After this operation meal ingestion still caused a decrease in plasma motilin levels. However, after a modified version of the operation was performed in 5 other dogs by which the upper half of the small intestine together with the duodenum was transected at the pyloric ring, plasma motilin was not suppressed by meal ingestion. The results suggest that motilin secretion is regulated by nutrieht ingestion and that the passage of nutrients through the duodenum plays an important role in its regulation.

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.

Effect of truncal vagotomy on intestinal phase of pancreatic polypeptide release in dogs.

In order to elucidate the role of the vagus nerve in the intestinal phase of pancreatic polypeptide (PP) release, mongrel dogs were given a 4-min intraduodenal infusion of saline, 20% glucose, or 10% soybean oil solution (50 ml each), before and one month after truncal vagotomy including pyloroplasty (TV). The saline infusion did not change the basal PP level, while the glucose infusion elicited a monophasic transient PP release, and the soybean oil infusion elicited a monophasic prolonged PP release in the intact dogs. The PP response following glucose infusion was almost abolished after TV, while the PP response to fat was attenuated, but a significant increase was nevertheless observed after TV. These results suggest that the vagus nerve has an important role in the intestinal phase of PP release and that other factors, e.g. hormonal, might also be involved in the regulatory mechanism, especially after fat loading.

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.

SUPPRESSIBILITY OF PLASMA MOTILIN BY ORALLY ADMINISTERED GLUCOSE IN PATIENTS WITH HYPERTHYROIDISM AND LIVER CIRRHOSIS

Plasma motilin levels were investigated. in normal subjects and patients with hyperthyroidism and liver cirrhosis by dextran-coated charcoal radioimmunoassay using a guinea pig antiserum raised against synthetic motilin. Fasting plasma motilin levels in normal subjects were widely distributed, ranging from less than minimal detectable level (50 pg/ml) to 485 pg/ml, with a mean (i SE) level of 224i 36 pg/ml. Patients with hyperthyroidism and liver cirrhosis also had widely scattered fasting motilin levels of 314156 pg/ml and 39l:l;71pg/ml, respectively. Following 50g oral glucose loading, plasma motilin levels gradually decreased in both groups. These results suggest that plasma motilin is suppressed by oral glucose loading in hyperthyroidism and liver cirrhosis.