Soichiro Morita

Discrepancies between the Doses of Cholecystokinin or Caerulein-Stimulating Exocrine and Endocrine Responses in Perfused Isolated Rat Pancreas

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.

Determination of Immunoreactive Somatostatin in Rat Plasma and Responses to Arginine, Glucose and Glucagon Infusion

SummaryA method for the determination of immunoreactive somatostatin in rat plasma is described. Blood specimens were collected into aprotinin and EDTA. Plasma was separated, immediately diluted with acidified acetone and ultrasonicated. The resultant supernatant was lyophilised. The dilution curve of the material thus extracted was parallel to that of synthetic somatostatin. The material was eluted mainly in a similar position to that of synthetic somatostatin on Sephadex G-25 (f) column chromatography. The somatostatin immunoreactivity was degraded significantly from the pre-incubated value of 846±86 pg/ml (n=4, mean±SEM) to 102±16 pg/ml in the same manner as that of synthetic somatostatin when incubated with one ml of fresh rat plasma at 37 °C for 30 min. The mean recovery in quadruplicate of immunoreactive somatostatin at concentrations of 100, 200 and 400 pg/ml was 83±7, 95±4 and 76±4%, respectively. Using this method, plasma immunoreactive somatostatin responses to arginine, glucose and glucagon infusion were measured in pentobarbital anaesthetized rats. The mean basal plasma immunoreactive somatostatin concentration in the jugular vein was 35±3 pg/ml (n=7), while that in the hepatic portal vein was 120±17 pg/ml (n=7). Infusion of arginine, glucose and glucagon all resulted in 2–3 fold increases in portal plasma immunoreactive somatostatin concentration.

Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus

Abstract This study reports the result of a 12-month, open-label multicenter study of the efficacy and tolerability of pravastatin in the management of hypercholesterolemia associated with non-insulin-dependent diabetes mellitus. Pravastatin produced a decrease, in 138 diabetic and 51 non-diabetic patients, in total serum cholesterol by 19 and 20%, in low-density lipoprotein (LDL) cholesterol by 25 and 29%, in apolipoprotein B by 15 and 19% and in triglycerides by 8 and 5%, respectively. High-density lipoprotein cholesterol levels were increased by 9% in both groups. All of these changes were significant ( P 1c levels and by the presence of hypertension or gross proteinuria, although a decrease in the two variables were less in those with body mass index ≥26.4 kg/m 2 or in those with age 1c levels in diabetic patients throughout the study. Pravastatin was generally effective in improving the serum lipids of hypercholesterolemic diabetic patients.

Clinical Features of Diabetes Mellitus in Japan

The first Symposium on Diabetes Mellitus in Asia was held in Kobe, Japan, in 1970 and the second symposium in Kyoto, Japan, in 1975. These two symposia raised many questions. Participants from various countries compared their findings on the frequency of diabetes and its complications. Such comparisons are usually complicated because of the differences in diagnostic criteria used, the age groups compared, and duration of diabetes observed, etc. In spite of these problems, careful analysis and close comparisons may offer important clues as to the pathogenesis of diabetes and the factors related to its complications. Japanese and Caucasian diabetes have some differences resulting from the Japanese diabetic pathophysiologic, ethologic, and ecologic factors. In this paper, diabetes is discussed from an ecologic viewpoint, especially characteristics of the disease and its prognosis in relation to the complications and food habits in Japan.

Monosodium glutamate (MSG) 投与による視床下部性肥満の膵-消化管ホルモンの動態

It has been reported that the neonatal administration of monosodium glutamate (MSG) in rodents produces lesions of the arcuate nucleus and the ventromedial nucleus of the hypothalamus and results in obesity in adulthood . Though there are a large number of reports using MSG-treated animals, most of them deal with neuronal and neuroendocrinological pathophysiology within the central nervous system. The present study, therefore, was designed to investigate the time-course of metabolic and hormonal changes in relation to the development of hypothalamic obesity induced by MSG in female Wister rats. In addition, responses of insulin and somatostatin to glucose loading were examined in rats with hypothalamic obesity . MSG, 2mg per g of body weight, was subcutaneously injected for 5 consecutive days after birth. Body weight, plasma glucose and immunoreactive insulin (IRI) were measured at oneto four-week intervals in rats aged from 6 days to 11 months. The Lee index, plasma triglyceride and immunoreactive glucagon (IRG) were measured at one-month intervals from one to 11 months. Immunoreactive somatostatin (IRS) and gastrin (IRGa) were determined at the 7th month or later. All parameters in plasma described above were assayed on samples drawn from the jugular vein. In addition, IRI and IRS in the pancreas were measured until 6 months. Further, responses of glucose, IRI and IRS to intragastric glucose loading (3g/kg body weight) were examined in portal plasma at the 11th month . All parameters in the MSG rats were compared with those in age-matched female controls which received the vehicle alone.

The Effect of COOH-terminal Peptides of Cholecystokinin on the Exocrine and Endocrine Pancreas in the Rat

Recently, the predominant molecular forms of cholecystokinin (CCK) in extracts of tissues from the central nervous system and small intestines of adult man and hog have been demonstrated to correspond to the COOH-terminal octaand tetra-peptide of CCK. CCK is one of the established gastro-intestinal hormones capable of stimulating pancreatic exocrine secretion. In addition, pure natural porcine CCK, synthetic COOH-terminal octa-peptide of CCK and synthetic caerulein which contains a COOH-terminal penta-peptide identical to CCK have been shown to stimulate insulin and glucagon secretion in vivo and in vitro. Thus, it seems reasonable to expect some effect of these COOH-terminal fragments of CCK on pancreatic exocrine and endocrine secretion. The present study was, therefore, undertaken to compare the various COOH-terminal fragments of CCK with those effects on pancreatic exocrine and endocrine secretion in the rat. Pancreases from male Wistar rats, fed ad libitum, were isolated according to the technique of Kanno. Perfusate consisted of a Krebs Ringer bicarbonate buffer containing 4.6% Dextran T-70 and 0.25% bovine serum albumin. The effects of various COOH-terminal peptides of CCK (synthetized by Prof. Noboru Yanaihara, Shizuoka) at the doses ranging from 10-II to 10-8M were studied in the presence of 50mg/d1 or 150mg/d1 glucose. Insulin (IRI) and glucagon (IRG) levels in the portal effluent were determined by radioimmunoassay using polyethyleneglycol and charcoaled dextran with antiserum 30K, respectively. Amylase activities in the pancreatic juice were assayed by a chromogenic method with blue-dyed starch polymer.