Search PubMed⌕ Search

Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 217 records · Page 12Linked to original sources

Diurnal profile of pancreatic exocrine secretion and plasma levels of gut hormones (cholecystokinin and pancreatic polypeptide).

We examined diurnal changes of pancreatic exocrine secretion and plasma levels of cholecystokinin (CCK) and human pancreatic polypeptide (hPP) in men with postoperative transient external pancreatic drainage (3 with pancreatico-jejunostomy: PJ, and 5 with pancreato-duodenectomy:PD). Plasma CCK levels increased and the pancreatic exocrine secretion showed a corresponding increase after meals in both groups. In the PJ group hPP levels increased after meals and there was a significant correlation between the plasma levels of CCK and hPP. In the PD group the plasma hPP levels were not detectable throughout the study and there was a better correlation between the exocrine secretion and the plasma CCK levels than in the PJ group. Plasma CCK levels showed rhythmic changes associated with pancreatic exocrine secretion, with no significant changes in plasma glucose and insulin in the night (24:00-07:00). These results suggested that (1) the resection of the pancreatic head which is rich in hPP contents led to a complete loss of anti-CCK effects on CCK, and that (2) fluctuation in plasma CCK levels, in the fasting state, might initiate pancreatic exocrine secretion.

Aged↗

Effects of proglumide on pancreatic endocrine and exocrine function in healthy humans.

A comparative study was done on the pancreatic endocrine (insulin (IRI), human pancreatic polypeptide (hPP] and exocrine secretion (fluid volume, amylase output, bicarbonate output), before and after administration of proglumide. At the time of the test meal loading, plasma hPP and cholecystokinin (CCK) were also measured. During continuous i.v. administration of proglumide 750 mg and 1650 mg/h 30 min before CCK-8 (20 ng/kg) stimulation, no significant difference in the rise of plasma hPP level was observed, as compared with a single stimulus of CCK-8, nor were there any significant differences in the exocrine secretion. The values of hPP and CCK-8 under a load of test meal significantly elevated after a food load. Although hPP showed a significant inhibition with the administration of proglumide 1650 mg/h, plasma CCK-8 and blood sugar levels were not significantly different from control groups. Therefore, while proglumide has a very weak effect on the action of pancreatic endocrine function, it does have an inhibitory effect on pancreatic function, during physiological stimulation.

Adult↗

In vitro study of cultured human insulinoma cells: evidence of abnormal sensitivity to glucose.

Human insulinoma cells were isolated and cultured in vitro, and their functional and morphological characteristics were determined. The cells, isolated as single cells or small cell clusters, reaggregated to almost the size of islets by the fifth culture day and were maintained in vitro for more than 1 month. Morphologically (light and electron microscopies) they were intact throughout the culture period. Immunohistochemically more than 50% of the cells in each reaggregate contained insulin. Incubation experiments revealed that a low glucose concentration (15 mg/dL) was sufficient to produce maximal insulin release. In the absence of glucose, 1 microgram/mL glibenclamide increased insulin release. On the other hand, 5 mM theophylline and 10 mM arginine did not alter insulin release significantly. Theophylline, arginine, and glibenclamide did not have any stimulatory effect on insulin release in the presence of 50 mg/dL glucose. Perifusion experiments with 50 mg/dL glucose disclosed a biphasic pattern of insulin release, and no significant change in insulin release occurred when the glucose concentration in the perifusate was switched from 50 to 150 and then back to 50 mg/dL. These findings demonstrate that human insulinoma cells can be isolated and maintained in vitro and that the cells have abnormal sensitivity to glucose.

Adenoma, Islet Cell↗

Effect of insulin on motilin release in man.

The effect of insulin on motilin release was investigated by use of the euglycemic glucose clamp technique. By use of this technique plasma glucose concentration was maintained constant at 80-90 mg/100 ml, and plasma insulin immunoreactivity (IRI) was increased from 15 +/- 6 microU/ml to 171 +/- 22 microU/ml in 10 min, and remained at this level for 2 hr. Plasma motilin like immunoreactivity (MLI) concentration decreased within 10 min from 199 +/- 36 pg/ml to 120 +/- 28 pg/ml and remained low during the course of study. A significant negative correlation between MLI and IRI concentrations (r = -0.72, p less than 0.01) was observed. The present results indicate that the suppressive effect of insulin on motilin release is a direct action of insulin and is not mediated by glucose.

Adult↗

Effect of methionine-enkephalin analog (FK 33-824) on plasma motilin.

In an attempt to elucidate the effect of opioid peptide on the secretion of various gastrointestinal hormones, the methionine-enkephalin analog, FK 33-824 (FK) was injected intramuscularly in healthy male adults. The plasma levels of motilin, gastrin and cholecystokinin were assessed by specific radioimmunoassay. After the injection of FK, the plasma level of motilin markedly decreased from the baseline value of 456 +/- 70.2 pg/ml to 264 +/- 44.7 pg/ml at 120 min. On the other hand, the plasma levels of cholecystokinin and gastrin remained unchanged. These data indicate that endogenous methionine-enkephalin may have an direct inhibitory effect on the secretion of motilin.

Adult↗

Elevated levels of serum pancreatic secretory trypsin inhibitor (PSTI) in patients with malabsorption syndrome.

Serum pancreatic secretory trypsin inhibitor (PSTI) was measured by radioimmunoassay in 5 patients with malabsorption syndrome. The serum level of PSTI was elevated to 123.8 +/- 25.8 ng/ml (Mean +/- SE) in patients with malabsorption syndrome, which was significantly higher than the 16.6 +/- 0.7 ng/ml level seen in 116 healthy control subjects. Serum PSTI levels in 5 patients with malabsorption syndrome showed inverse correlations with serum levels of cholesterol, cholinesterase and amylase, and not with serum levels of vitamin E, carotene, apoprotein A-IV, albumin, nor with immunoreactive elastase 1, respectively. These results suggest that elevated levels of serum PSTI represent a state of malnutrition due to impaired intestinal absorption.

Adult↗

Aberrant insulinoma in the duodenum.

A rare case of aberrant insulinoma in the duodenum is described. Hyperinsulinemia with typical hypoglycemic symptoms was induced by prolonged fasting. Selective angiography demonstrated a tumor supplied from the first branch of the jejunal artery, and duodenoscopy revealed a submucosal tumor at the third portion of the duodenum. An increase in venous plasma immunoreactive insulin concentration was evident in the vein draining from the tumor, by sampling through percutaneous transhepatic catheterization. Hypoglycemia was ameliorated after the removal of the submucosal tumor of the duodenum. Histologic and immunocytochemical characterization of the tumor showed an insulinoma, predominantly composed of cells with typical B-cell-like granules. The acid extract of the tumor contained 1.2 U/g of insulin, and this insulin, analyzed by reverse-phase high-pressure liquid chromatography, revealed that it had the same amino acid structure as that of human insulin.

Adenoma, Islet Cell↗

High plasma cholecystokinin response following ingestion of test meal by patients with non-insulin dependent diabetes mellitus.

Postprandial responses of plasma cholecystokinin (CCK) in patients with non-insulin dependent diabetes mellitus (NIDDM) were studied with a CCK specific radioimmunoassay. After the ingestion of a liquid test meal, plasma CCK levels increased from the basal level of 9.8 +/- 1.1 pg/ml to a peak of 19.4 +/- 1.8 pg/ml at 20 min in healthy subjects (n = 10). The ingestion of a test meal in patients with NIDDM (n = 10) resulted in a significantly greater increase of plasma CCK than in healthy subjects and a significant increase of plasma CCK from a basal level of 14.2 +/- 4.4 pg/ml to a peak of 47.4 +/- 12.4 pg/ml at 10 min.

Adult↗

Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Blood Glucose↗

Plasma somatostatin-like immunoreactivity responses to a mixed meal and the heterogeneity in healthy and non-insulin-dependent (NIDDM) diabetics.

Peripheral plasma somatostatin-like immunoreactivity (SLI) was estimated in non-extracted plasma using a specific somatostatin-14 (SS-14) antiserum. The basal plasma SLI level in healthy subjects (n = 18) was 43 +/- 2.9 pg/ml (mean +/- SE) and rose significantly to 8.3 +/- 2.7, 7.3 +/- 1.1 and 5.8 +/- 2.1 pg/ml above the mean basal level 20, 30, and 40 min after a mixed meal, respectively (P less than 0.05). Basal plasma SLI levels in diet (n = 8), sulfonyl urea (n = 8), and insulin groups (n = 8) of non-insulin-dependent maturity onset diabetics (NIDDM) were 50 +/- 1.6, 59 +/- 4.5, and 74 +/- 5.8 pg/ml, respectively. The basal levels for patients with NIDDM were significantly higher than those for healthy subjects (P less than 0.05). No significant increases in plasma SLI were observed after a mixed meal in any group of NIDDM subjects. Elevated plasma SLI levels are considered to be closely related to the severity of the diabetes. The ratios of SS-14 and SS-28 to the total amount of basal plasma SLI were analyzed using high pressure liquid chromatography (HPLC). The ratio of SS-14 to the total SLI was 71-80% in healthy subjects. The ratio of SS-28 to the total SLI increased from 26-30% in the diet group to 50-55% in the group on insulin. These findings suggest a possible pathophysiological role for gastrointestinal somatostatin in NIDDM.

Adult↗

Comparisons between absorption of vitamin E in patients with chronic pancreatitis and healthy controls: the bioavailability of vitamin E.

The fasting serum levels of alpha-tocopherol were determined by high-pressure liquid chromatography in 13 patients with chronic pancreatitis of whom 7 were positive for pancreatic calcification (CCP) and 6, negative (NCP) and 10 healthy subjects. The fasting serum levels of alpha-tocopherol were significantly lower in patients with chronic pancreatitis (7.2 +/- 1.1 micrograms/ml for CCP and 7.9 +/- 0.6 for NCP) than in healthy subjects (11.3 +/- 0.7 micrograms/ml). Vitamin E absorption was determined in those with chronic pancreatitis and in healthy subjects after postprandial oral administration of 400 mg of vitamin E, using soft capsules which contained tocopherol nicotinate along with an appropriate amount of a suspension of an ester of fatty acids with glycerol and middle chain triacylglycerol. The mean absorption of vitamin E was 12.7 +/- 2.0 micrograms/ml X hr for healthy subjects, 9.1 +/- 3.1 micrograms/ml X hr for CCP and 13.0 +/- 2.7 micrograms/ml X hr for NCP, respectively. There was no significant difference in vitamin E absorption between patients with chronic pancreatitis and healthy subjects. Further, the rate of hydrolysis of tocopherol nicotinate did not significantly differ between healthy subjects and patients with chronic pancreatitis. It is of interest to note that vitamin E absorption in patients with chronic pancreatitis was increased by the postprandial use of an oily suspension type preparation of tocopherol nicotinate.

Administration, Oral↗

Effects of cisapride on the secretion of pancreatic polypeptide in healthy volunteers.

Plasma human pancreatic polypeptide (hPP) responses to intravenous injections of a new gastric and intestinal motility promoting agent, R51 619 (cisapride), were studied in healthy volunteers. The mean fasting concentrations of plasma hPP (39 +/- 5.4 pg/ml; mean +/- S.E.) were elevated significantly to the peak values of 118 +/- 25.1 pg/ml 30 min after the drug had been given in a dose of 4 mg over 5 min. However, plasma insulin (IRI), glucose and prolactin levels were not elevated. Atropine diminished the cisapride-induced hPP elevation, thereby suggesting that cisapride induced release of acetylcholine but had no antidopaminergic action.

Adult↗

High plasma cholecystokinin levels in patients with chronic pancreatitis having abdominal pain.

Plasma cholecystokinin (CCK) responses after ingestion of a test meal in patients with mild chronic pancreatitis having abdominal pain were studied with a radioimmunoassay using the CCK specific antiserum (OAL-656) produced by a novel immunization procedure. Mean concentration of the fasting plasma CCK determined using CCK-8 as a standard was 31.5 +/- 5.8 pg/ml in six patients who had mild impaired exocrine function with pain, and was significantly higher than 10 healthy subjects (9.8 +/- 1.8 pg/ml). In those patients, the ingestion of a liquid test meal led to a peak of 75.1 +/- 25.4 pg/ml at 30 min, and the 120-min integrated CCK response (5427 +/- 1217.3 pg X min/ml) was significantly higher than in healthy subjects (1538 +/- 110.1 pg X min/ml).

Abdomen↗

Influence of methionine-enkephalin analogue (FK-33-824) on the secretion of pancreatic hormones.

To determine the effects of methionine-enkephalin on secretion of pancreatic hormones, five healthy male adults were intramuscularly given 0.5 mg of FK 33-824, a methionine-enkephalin analog and blood levels of pancreatic hormones were measured at different time intervals. FK 33-824 significantly lowered basal levels of plasma insulin (IRI) and pancreatic polypeptide and decreased IRI secretion in 75 g-OGTT. It also delayed the elevation of blood sugar level in 75 g-OGTT. No change occurred in the basal levels of plasma glucagon, somatostatin and blood sugar. These results imply that methionine-enkephalin in the pancreas and alimentary tract may act as an inhibitor on the secretion of insulin and pancreatic polypeptide and hence relates to the absorption of sugar.

Adult↗

Appearance mechanism and molecular heterogeneity of serum pancreatic secretory trypsin inhibitor (PSTI).

Serum immunoreactive pancreatic secretory trypsin inhibitor (PSTI) was measured by RIA. Serum PSTI levels were elevated in case of acute pancreatitis (15 of 15 cases: 317.7 +/- 155.6 ng/ml: Mean +/- SE) or pancreatic carcinoma (16 of 25 cases; 71.8 +/- 17.1 ng/ml), and in those with chronic renal failure (6 of 6 cases: 412.8 +/- 98.2 ng/ml). The molecular heterogeneity of elevated serum PSTI n such diseases was studied using chromatofocusing column chromatography. The results showed that serum PSTI was free from trypsin(-ogen) and was composed of at least three molecular forms of different isoelectric points. Two major forms were eluted around pH 8.2 (peak I) and 7.5 (peak II), with one minor form around pH 6.9 (peak III) from the column. The relative ratio of three forms differed with the disease state. Peak I was high in patients with pancreatic carcinoma, and peak II was high in patients with acute pancreatitis.

Acute Disease↗