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Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 235 records · Page 13Linked to original sources
PubMed1985

Effect of somatostatin and its analogs on histamine-stimulated cAMP production in isolated guinea pig gastric glands.

The effect of somatostatin-14 (ss-14), somatostatin-28 (ss-28), and [D-trp8]somatostatin-14 ([ D-trp8]ss-14) on both histamine-stimulated cellular cAMP production and [3H]-cimetidine binding on plasma membranes in isolated guinea pig gastric glands was investigated. These three peptides partially inhibited (approximately 50% maximally) the increase of cAMP production stimulated by histamine. There was no inhibition of [3H]-cimetidine binding on plasma membranes from these isolated gastric glands. These results indicate that somatostatin acts directly on parietal cells and inhibits histamine-stimulated cAMP production with no influence on H2 receptor in histamine stimulated gastric secretion. Inhibitory potency of somatostatin and its analogs against histamine-stimulation may be equal at the cellular level.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Plasma motilin concentration and interdigestive migrating motor complex in diabetic gastroparesis: effect of metoclopramide.

The objective of this study is to determine whether abnormal rhythm and amplitude of the oscillation in plasma motilin concentration are responsible for the abnormal motility observed in patients with diabetic gastroparesis. We also investigated the effect of metoclopramide on plasma motilin concentration and gastrointestinal motility in these patients. In healthy controls, basal plasma motilin concentration fluctuated in phase with the interdigestive migrating motor complex. All patients with diabetic gastroparesis did not have antral phase III activities and had significantly higher basal motilin concentrations, which maintained a normal oscillatory pattern. Administration of metoclopramide initiated antral phase III activities in healthy controls and in patients with diabetic gastroparesis. These were accompanied by a concurrent rise in plasma motilin concentration in healthy controls, contrasting with a fall in plasma motilin concentrations in patients with diabetic gastroparesis. We conclude that diabetic gastroparesis is associated with absence of antral interdigestive migrating motor complex and with elevated plasma motilin concentration with normal cyclic fluctuations. Our studies also show that metoclopramide initiates antral phase III activities in diabetic gastroparesis independent of plasma motilin concentration.

Adolescent↗
PubMed1985

Plasma apolipoprotein A-IV levels decrease in patients with chronic pancreatitis and malabsorption syndrome.

An immunochemical method was developed for measurements of serum levels of apolipoprotein A-IV (apo A-IV). Using this technique, we found decreased levels of apo A-IV in patients with chronic pancreatitis and malabsorption syndrome and these low levels of apo A-IV in a patient with malabsorption syndrome were overcome after appropriate oral nutrition. Thus, measurements of apo A-IV may provide a good index for the assessment of fat intake and absorption.

Adolescent↗
PubMed1985

Changes in insulin secretion after secretin administration and the implications in diabetes mellitus.

Secrepan (Eisai Co. Tokyo, Japan) was administered to 9 healthy volunteers and 36 patients with non-insulin dependent diabetes mellitus (NIDDM) to clarify the effect of secretin on the pancreatic B-cell, by determining the changes in blood of insulin (IRI). Whereas IRI in healthy subjects showed a monophasic change, reaching a peak (delta IRI = 43 +/- 7.3 microunits/ml, M +/- SE) 5 min after secretin loading and returning to the basal level in 15 min, NIDDM patients on diet therapy (delta IRI = 40.2 +/- 7.6 microunits/ml) showed no significant difference from the control group, but NIDDM patients on sulfonylurea (SU) (15.5 +/- 2.4 microunits/ml) and those on insulin therapy (5.3 +/- 1.4 microunits/ml), both showed a significant depression in responsiveness. Further, the changes in insulin secretion after atropine administration in healthy subjects and the changes in IRI response to Secrepan in vagotomized patients were also determined. As a result, data which preclude the possibility of association of the vagus nerve and cholinergic nerve with the stimulation of insulin secretion by secretin were obtained, and a direct action of secretin on the cell of islets of Langerhans was suggested. The maximum IRI response after a secretin load had a significant positive correlation with the IRI response after a 75-gm GTT and the content of C-peptide immunoreactivity in 24-hour urine. Therefore, insulin response to a secretin load can be useful in assessing endogenous insulin secretion and provides a pertinent clinical guide for the selection of an appropriate therapy for diabetes mellitus.

Adult↗
PubMed1985

Identification of insulin variants in patients with hyperinsulinemia by reversed-phase, high-performance liquid chromatography.

We have characterized the molecular forms of circulating insulins in patients with hyperinsulinemia of diverse etiology. We have also compared the efficacy of various chromatographic conditions using reversed-phase (RP) HPLC. Using 0.2% trifluoroacetic acid (TFA) and triethylamine (TEA) with acetonitrile as the organic modifier, at an elution rate of 0.17%/min, porcine, bovine, and human insulins could be easily separated as well as abnormal insulins in the plasma of a patient (J.R.) with hyperinsulinemia of unknown etiology. When the reversed-phase C18 column was changed and a gradient of 0.33%/min was used, the abnormal insulin in patient J.R. could not be separated. By changing the solvent system to acetonitrile and isopropanol (vol:vol, 3:1) containing 0.1% TFA, omitting the TEA, and using a gentle gradient of 0.1%/min, various semisynthetic analogues of human insulin could be easily separated and the abnormal insulin could be identified in the plasma of the patient J.R. Abnormal insulin was also found in a patient with MEN-I, but in contrast, the insulins in eight patients with benign sporadic insulinomas appeared to be normal. These results suggest that certain hyperinsulinemic states may be associated with an abnormal insulin and that RP-HPLC is useful for identification of insulin variants in the circulation. However, the conditions of RP-HPLC may be critical if the abnormalities of the insulin are subtle.

C-Peptide↗
PubMed1985

Diurnal profile of plasma motilin concentrations during fasting and feeding in man.

Oscillations in basal plasma levels of the pancreatic hormones; insulin, glucagon and pancreatic polypeptide have been reported previously. We now report on oscillations in circulating motilin-like immunoreactivity (MLI) in fasted and fed man. Six healthy subjects were studied during two 36-hour test periods, one while fasting and another with the regular ingestion of equicaloric meals at 0800, 1200 and 1800 hours. Blood was sampled every 30 min. from 0800 to 2400 and every 60 min. from 2400 to 0800 the next morning. In the fasting state the mean +/- S.E. concentrations in plasma for the 6 subjects were: MLI, 180 +/- 19.4 pg/ml, insulin 4.4 +/- 1.1 microU/ml, pancreatic polypeptide (hpp), 119 +/- 25.0 pg/ml, and glucose 82 +/- 6.4 mg/dl. Large oscillations in plasma MLI were detected with 1/2 amplitude of 23.2 +/- 4.7% of mean, and a period of 159 min. which varied according to each subject. Plasma hpp levels fluctuated similarly, and a good correlation was found between MLI and hPP indicating a rhythmic secretion of these peptides by the gut and pancreas. MLI fluctuations were independent of insulin which revealed a significant oscillation with a period of 320 min. The ingestion of meals caused the expected increase in circulating levels of insulin, hPP, and glucose. In contrast a decrease in the concentration of MLI was observed. An inverse correlation was found between MLI and glucose and between MLI and insulin. Thus, fasting is associated with large oscillations of motilin, the gut motility hormone, which are suppressed by feeding. The increase in glucose and/or insulin may be important in suppressing motilin secretion during feeding.

Adult↗
PubMed1985

Low plasma cholecystokinin response after ingestion of a test meal in patients with chronic pancreatitis.

Postprandial responses of plasma cholecystokinin (CCK) in patients with severe chronic pancreatitis (n = 7) were studied. Plasma CCK level rose from 11.2 +/- 1.8 pg/ml at the basal level to a maximum of 23.3 +/- 3.0 pg/ml at 10 min after the ingestion of a liquid meal in healthy subjects (n = 6). However, such significant plasma CCK response to the meal was not observed in patients with chronic pancreatitis in whom CCK levels rose from a basal level of 9.7 +/- 0.91 pg/ml to a peak of 13.8 +/- 1.6 pg/ml at 60 min. It is suggested that the low response of CCK after the meal might reflect impaired function of the enteropancreatic axis to intraluminal stimuli in patients with severe chronic pancreatitis.

Adult↗
PubMed1983

Cholinergic independent dopaminergic regulation of motilin release in man.

This study investigated the dopaminergic control of motilin secretion in normal volunteers. Dopamine infusion caused a significant decline of plasma motilin levels, but had no effect on human pancreatic polypeptide (hpp) secretion. Dopamine antagonism with domperidone resulted in a significant elevation of motilin 10 and 20 min after the drug administration, and a significant elevation of hpp at 20 and 30 min. Atropine suppressed the basal levels of motilin and hpp but did not alter the increment of motilin levels after domperidone administration, while atropine suppressed domperidone induced secretory response of hpp. These results suggest that dopaminergic mechanisms exert a tonic inhibitory effect on motilin secretion in normal subjects.

Adult↗
PubMed1983

Evidence for modulation of motilin secretion by pancreatico-biliary juice in health and in chronic pancreatitis.

The gut hormone motilin can initiate the interdigestive migrating motor complex. There are synchronous cyclic changes in plasma motilin-like immunoreactivity (MLI) levels and pancreatico-biliary secretion during the interdigestive period which may be causally related. The purpose of this study was to investigate the role of pancreatico-biliary secretion into the gut as a modulator of plasma MLI concentrations. In six healthy subjects, the mean basal plasma MLI level was 130 +/- 16 pg/ml. Infusion of cholecystokinin octapeptide (CCK-8) stimulated MLI secretion, with an integrated (30 min) response of 2028 +/- 340 pg/min X ml. Intraduodenal perfusion of pancreatico-biliary juice produced a similar increase in plasma MLI, with a 30 min integrated response of 2190 +/- 270 pg/min X ml. Neither enzyme activity, osmolarity, or pH accounted for the response. In six patients with exocrine pancreatic insufficiency, although their mean basal plasma MLI concentration of 205 +/- 44 pg/ml was significantly higher than that observed in healthy subjects, there was no significant plasma MLI increase after CCK-8 infusion. Pancreatic exocrine secretion was severely compromised in these patients, as evidenced by the markedly reduced peak lipase (3.8 +/- 0.6 kU/h) and trypsin (2.4 +/- 0.5 kU/h) outputs. In contrast, infusion of pancreatico-biliary juice obtained from healthy subjects caused a rise in plasma MLI, with a 60 min integrated response of 3912 +/- 1031 pg/min X ml, which was similar to that of 3947 +/- 472 pg/min X ml in healthy subjects. We conclude that there is an undefined factor in pancreatico-biliary juice that stimulates MLI release. A deficiency of pancreatic exocrine secretion may be responsible for the impaired MLI response to CCK-8 stimulation in chronic pancreatitis. Since MLI is known to initiate the formation of the interdigestive migrating motor complexes, diminished motilin release secondary to pancreatic exocrine deficiency may result in disordered gastrointestinal motor activity in patients with chronic pancreatitis.

Adolescent↗
PubMed1982

Evidence for cholinergic and vagal noncholinergic mechanisms modulating plasma motilin-like immunoreactivity.

Basal concentrations of plasma motilin-like immunoreactivity (MLI) and responses to insulin-induced hypoglycemia were measured in healthy subjects (n = 13) in diabetics with clinical evidence of autonomic neuropathy (AN; n = 7), in diabetics without AN (n = 9), and in five recently (6--12 months) vagotomized subjects. Mean basal MLI concentrations were similar in the healthy subjects (141 +/- 21.5 pg/ml) and diabetics without AN (124 +/- 22.4 pg/ml), but were significantly higher in diabetics with AN (349 +/- 71.5 pg/ml) and in vagotomized subjects (381 +/- 47.6 pg/ml). In both healthy subjects and diabetics without AN, the acute administration of insulin (0.1--0.2 U/kg) caused a fall in the mean MLI concentration, reaching a nadir within 20 min, returning to the basal concentration by 60 min, and rising above basal levels by 90 min. In diabetics with AN and vagotomized subjects, the fall in MLI persisted for 90 min. Intravenous atropine administered 15 min after the insulin injection in healthy subjects did not impair the return to basal. The responses were not related to the degree of hypoglycemia, the absolute or relative fall in blood glucose concentrations, or differences in blood glucose among healthy subjects, diabetics, or vagotomized subjects. It appears, therefore, that insulin lowers plasma MLI levels, which are restored to basal by a vagal noncholinergic mechanism. Furthermore, the vagus exerts a suppressive effect on basal MLI levels, and vagotomy and diabetic autovagotomy are associated with abnormal elevation of MLI levels. Since motilin is thought to be important in interdigestive intestinal motility, abnormalities in MLI secretion in diabetics with autonomic neuropathy may contribute to gastrointestinal stasis and erratic diabetic control.

Atropine↗