Katsuhiro Terashi

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.

Effects of tris(hydroxymethyl)aminomethane on biosynthesis and release of insulin in the pancreatic Langerhans islets

Tris(hydroxymethyl)aminomethane (Tris) has been shown to inhibit selectively the Golgi apparatus and Golgi-endoplasmic reticulum-lysosomal system (GERL system) of several kinds of cells including pancreatic B cells. This study was designed to assess the effect of Tris on insulin, glucagon and somatostatin release and insulin synthesis in pancreatic B cells by using isolated rat pancreatic islets. Tris suppressed glucose-induced insulin release, whereas it did not affect the glucagon and somatostatin release. Furthermore, the incorporation of [3H]leucine into the insulin fraction was suppressed by 10 mM Tris, but the sum of the radioactivity of both proinsulin and insulin fraction were not influenced. The present study suggests that the Golgi apparatus and GERL system may play a role in insulin secretion and biosynthesis in pancreatic B cells.

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.