The role of glucagon-insulin interactions in control of glucose turnover and its significance in diabetes.
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Animals↗
Biomedical subjects
K Doi
Publications and source records attributed to K Doi.
Extrapancreatic glucagon in the dog.
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Animals↗
Comparison of image quality obtained with optical and radiographic magnification techniques in fine-detail skeletal radiography: effect of object thickness.
High-resolution radiography may be done using either optical or radiographic magnification. In the former technique, industrial Type M film was used without screens and the image was viewed with 4-10X optical magnification. In the latter technique, RP film was used with Detail screens and 4X geometric magnification together with a microfocus x-ray tube having a nominal focal spot size of 50 mum. The imaging properties of both techniques were evaluated by means of H & D curves, modulation transfer functions, and Wiener spectra. It was found that for thin objects such as the hand, optical magnification provides better bone images than radiographic magnification; whereas for thicker parts such as the knee, radiographic magnification is superior.
Bone and Bones↗
Effects of diets on cold tolerance and metabolic responses to cold in fasted rats.
Effects of high-fat and high-protein diets on cold tolerance in fasted rats were investigated. High-fat diets caused significant increases in body weight, blood-free fatty acids (FFA), ketone bodies and glucose, while high-protein diet did not modify any of these parameters. Rats on high-fat diets that were exposed to cold after clipping exhibited an intermediate cold tolerance as assessed by the rate of fall in colonic temperature between control rats on a standard diet and cold-acclimated rats. The extent of increase of blood FFA and decrease of blood glucose due to cold exposure was less in the high-fat diet group than in control group, but greater than in cold-acclimated group. The lower fall in colonic temperature due to cold exposure was signifcantly associated with less increase in blood FFA and less decrease in blood glucose. In this relation the high-fat diet group was also intermediate between the control and cold-acclimated groups. The high-protein diet did not make any difference in cold tolerance and cold-induced changes in blood metabolites as compared with those in control standard diet, although it resulted in a marked increase in urinary nitrogen excretion. These results indicate that a high-fat diet could exert a significant favorable effect on cold tolerance in fasted rats, but the effect would not be as much as as in cold acclimated rats.
Adaptation, Physiological↗
Measurement and partial characterization of immunoreactive glucagon in gastrointestinal tissues of dogs.
We have reported previously that increasing amounts of immunoreactive glucagon (IRG), measured by four specific antisera, appeared in plasma of depancreatized insulin-deficient dogs. It was therefore concluded that pancreatectomy was not accompanied by glucagon deficiency in the dog, but instead excessive amounts of extrapancreatic IRG could contribute to the diabetic syndrome. In order to locate the source of extrapancreatic glucagon, tissue extracts were assayed with anti-glucagon sera 30-K and K-44, which cross-react minimally with crude gut extracts. IRG was detected in all gastrointestinal tissues and in the salivary glands, but not in extracts of liver, kidney, brain, heart atrium, and adenohypophysis. Immunologic dilution curves of extracts from all gastrointestinal tissues were parallel to those of the pure pancreatic glucagon standard, and both antisera (30-K and K-44) measured the same concentrations. The highest concentration of gastrointestinal IRG was found in the fundus and corpus of the stomach. Presence of IRG in gastrointestinal tissues of depancreatized dogs indicates that gastrointestinal cells can not only secrete but also store large amounts of IRG. Extracts of mucosa of stomach fundus were further purified by gel filtration on Biogel P-30 columns. The immunoreactivity in the eluate was assayed by 30-K and a strongly crossreacting antibody, K-4023. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was found to contain the largest amount of IRG and the highest specific immunoreactivity (IRG/protein concentration). This fraction showed also the highest activity in a glucagon-receptor assay system. Disc gel electrophoresis in the presence of urea resolved this fraction into three immunoreactive components, one of which was identical to pancreatic glucagon in its electrophoretic mobility. It appears, therefore, that mucosa of the upper stomach in the dog contains a polypeptide similar to pancreatic glucagon. We conclude that (a) hyperglucagonemia in the dog can result from excessive secretion of IRG not only by the pancreatic alpha cells but also by cells of the gastrointestinal tract; (b) the highest IRG concentration was found in fundus and corpus of the stomach and lower concentrations throughout the gastrointestinal tract; (c) the IRG component in the stomach displayed immunologic and physical properties similar to pancreatic glucagon.
Animals↗
Changes of blood pressure, plasma renin activity and plasma aldosterone concentration following the infusion of Sar1-Ile8-angiotensin II in hypertensive, fluid and electrolyte disorders.
1-Sarcosine, 8-isoleucine angiotensin II (Sar1-Ile8-AII) was infused intravenously in 5 normal volunteers and 66 subjects with various hypertensive, fluid and electrolyte disorders. Changes of blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were studied. In normal subjects, Sar1-Ile-AII showed pressor (agonistic) activity, which was related to both dosage and sodium intake. Hyporeninaemic hypertensive subjects (pirmary aldosteronism) showed pressor responses to a smaller dose of this compound than the dose employed in normal subjects. Hyporeninaemic hypertensive subjects and normal volunteers after 3 days of high sodium intake showed significant elevations of BP and PAC and reduction of PRA. Changes of BP, PAC and PRA in normoreninaemic subjects including those with Bartter's syndrome, renal tubular acidosis or liver cirrhosis with ascites showed reduction of BP and PAC and elevation of PRA. The results indicate that the compound has both agonistic and antagonistic activities for blood pressure; which of these is obtained apparently depends upon endogenous angiotensin II levels, as well as the dosage employed. The results in subjects with high and low PRA suggest that the compound has antagonist and agonist actions at 3 sites of angiotensin II action, i.e. peripheral vascular bed, renin release mechanism from juxta-glomerular apparatus and the zona glomerulosa of the adrenals.
Acidosis, Renal Tubular↗
Pathogenicity for chicks of line cells from lymphoma of Marek's disease.
Pathogenicity for chicks of the MSB-1 line, a cell line derived from the tumorous tissue of a chick with Marek's disease (MD) and established by Akiyama & Kato, was studied. Five groups, including a control one, of 20 chicks each were inoculated with 1 X 10(3), 1 X 10(4), 1 X 10(5), 1 X 10(6) and no cells of a 180-day culture of the cell line at one day of age. They were housed all together in an isolation unit. An attempt was first made successfully to isolate MD virus (MDV) directly in culture of kidney cells 3 weeks after inoculation. Horizontal infection was first detected 4 weeks after inoculation. From 3 weeks after inoculation on, the disease with almost the same clinical and pathological pictures as the infection with a virulent strain of MDV showed a high incidence. Morbidity was closely related to the number of MSB-1 line cells inoculated. Parenchymal destruction was conspicuous in the central lymphoid organs of four chicks given the largest number of MSB-1 line cells and sacrificed in extremis about 4 weeks after inoculation. Establishment of MD in chicks inoculated with MSB-1 line cells carrying MDV genome seemed to be initiated under the circumstances where the line cells which had come into contact with susceptible cells in the peritoneal cavity released virulent MDV per se. Then host chicks might be infected with MDV and suffer from MD at a high rate. There was no great difference in oncogenic potential between MSB-1 line cells cultivated in vitro for 180 days and virulent MDV serially passaged through one-day-old chicks.
Animals↗
Fine structure of epithelial cells of Lieberkühn's crypts in feline panleukopenia.
Electron microscopic observation was carried out on epithelial cells of Lieberkühn's crypts of cats naturally affected with feline panleukopenia. The most important change was the replication of feline panleukopenia. The most important change was the replication of feline panleukopenia virus in the nucleus with associated alterations in the lining epithelial cells of the crypts. In these cells in the early stage of infection, virus particles 20 nm in average diameter were found either singly or in small regularly arrayed clusters everywhere in the markedly swollen nucleus. In the course of infection, the nucleus of infected cells became rather atrophic with a marked margination of chromatin granules. Its major portion was occupied with masses of fine fibrillar substance. It was a "viral matrix area" in which appeared a large compact aggregate of virus particles showing a crystalline array. At the same time, the outer membrane of the nuclear envelope partially extended and disrupted. Membranous elements related to it in the cytoplasm were regularly distributed almost always with particles indistinguishable from the virus particles in the nucleus. From these results it was suggested that the major portion of the infected nucleus, or the site of viral replication, might correspond to the amphophilic intranuclear inclusion body revealed by light microscopy.
Animals↗
[Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)].
The present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin. Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds. Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs. Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response. It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas. Forty-eight hours after injection, the animals were completely diabetic. Light- and electron-microscopic exadminations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells. 1egenerative and necrotic changes were also seen in a few alpha-cells. These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight. Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT: 3g/kg). Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals. It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine. Pre-treatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective. N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity. It seems that streptozotocin interfers with NAD formation in the beta-cell. Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.).
Adenoma, Islet Cell↗
[Simultaneous measurements of free thyroxine and triiodothyronine fractions in human serum by means of equilibrium dialysis (author's transl)].
Simultaneous measurements of serum free thyroxine (T4) and triiodothyronine (T3) fractions were studied using a modification of equilibrium dialysis described by Sterling and Brenner. To 1.2 ml of the serum to be assayed, 131I-T4 and 125I-T3 were added in a concentration of 2 mug/dl and 25 ng/dl, respectively, both of which were preliminarily dialysed according to Schussler and Plager. Half ml of the serum with tracers added was dialysed against 9 ml of phosphate buffer (ionic strength 0.15, pH 7.4) for 18 hours at 37 degrees C and 0.1 ml was reserved from the rest in a counting tube (in duplicate). After the completion of dialysis, the dialysate was mixed with 1 ml of pool serum and the contaminating inorganic iodide (in the form of 131I or 125I) was eliminated by adsorption on anion exchange resin. The radioactivity of 3 ml of the dialysate and 0.1 ml of the preserved serum (with the tracers added) was counted and the free (or dialysable) fractions were expressed as a ratio of the count of the former divided by that of the latter adjusted to an equal volume by calculation. The amount of either T4 or T3 added as tracers had no influence on free T4 or T3 fraction unless either of them was added to a concentration of 10 mug/dl. When 125I-T3 of low specific activity (50 muCi/ug) was used as a tracer, free T3 fraction measured simultaneously with free T4 fraction tended to be higher than that measured with a single tracer. When 125I-T3 of higher specific activity (300 muCi/mug) was employed, free T3 fraction obtained with two methods did not differ significantly. Using serum T4 and T3 concentrations measured by competitive protein binding analysis and radioimmunoassay, respectively, the free T4 and T3 concentrations were estimated with sera of normal, hyperthyroid, hypothyroid and uncomplicated pregnant subjects.
Adsorption↗
Effect of focal spot distribution on blood vessel imaging in magnification radiography.
From a computer simulation study of blood vessel imaging with uniform, triangular, gaussian, and twin gaussian line spread functions (LSF) corresponding to various focal spot distributions, it is found that vessel images magnified less than 6 times are not strongly dependent upon the focal spot distributions when the size of the focal spot is equal to or smaller than the vessel diameter. When the focal spot is larger than the vessel, image distributions vary appreciably with focal spot distributions, except at low magnification. It is concluded that, in many practical cases, the focal spot distribution does not seriously affect magnified image distributions of blood vessels.
Angiography↗
Longitudinal magnification in radiologic images of thick objects: a new concept in magnification radiography.
New concepts which are useful for evaluating image resolution and distortion in magnification radiography are introduced. It is shown theoretically and experimentally that "longitudinal magnification" defined as the ratio of the magnified image size to the conventional image size for objects located in a plane perpendicular to the film, is given approximately by the square of the conventional magnification. Resolution in the radiographically magnified image of such objects is much higher than that obtained by optical magnification. This is confirmed experimentally by radiographs of square-wave test objects. The related image distortion is also discussed.
Mathematics↗
Effect of some cationic drugs on the intestinal absorption of pralidoxime iodide.
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Amines↗
[Feline viral rhinotracheitis in Japan--Isolation of herpes type virus and pathologic picture (author's transl)].
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Animals↗
Cyclical effects of triiodothyronine on blood-free fatty acid and glucose concentrations in warm-adapted and cold-adapted rats.
Effects of triiodothyronine (T3) (100 mug/100 g, sc) on blood-free fatty acid (FFA) and glucose concentrations were investigated in warm- and cold-adapted rats. Blood specimens were obtained from the tail locally anesthetized with lidocaine. In warm-adapted rats FFA rose 3 to 6 hr after administration of T3, but returned to the pre-injection level 12 hr later. Thereafter, blood FFA level showed a repeated cyclical rise and fall every 12 hr for up to 60 hr, while blood glucose level did not increase until 12 hr later and this level was maintained for up to 36 hr. After that time it also showed a repeated rise and fall every 12 hr for up to 60 hr. Both FFA and glucose levels returned to the initial values after 72 hr. Changes induced by T3 in blood levels of these metabolites were reciprocal. In cold-adapted rats the patterns of responses to T3 were essentially the same as those observed in warm-adapted ones, except that T3 provoked a simultaneous rise in blood glucose as well as FFA 6 hr after injection, although an extent of FFA increment was less than in warm-adapted rats. Reserpine pre-treatment caused a considerable reduction in the FFA mobilizing action of T3. The FFA and glucose mobilizing action of T3 was also observed at dosages of 25 and 6.25 mug/100 g, although to lesser extent. These results indicated for the first time the cyclical action of T3 on blood FFA and glucose concentrations, and a changed sensitivity to T3 in cold-adapted animals.
Acclimatization↗
In vivo lipolytic effect of glucagon in warm-adapted and cold-adapted rats.
In vivo effect of glucagon on blood-free fatty acid (FFA) concentration was investigated in rats adapted to 25 degree C and to 5 degree C. Intraperitoneal injection of glucagon in 100 or 25 mug/100 g body weight doses was followed by a triphasic response in blood FFA concentration: an immediate and marked rise at 5 min, a secondary depression at 60 min and a final rise at 120 to 240 min after the injectionss. For the 12.5 and 6.25 mug/100 g body weight injections, an initial increment was significantly lowered and no elevation at 240 min was observed. Concomitant elevations of blood glucose concentration were shown 5 min after glucagon injection of 100, 25, 12.5, and 6.25 mug/100 g body weight doses and their extents were not significantly different each other between these doses. However, rise in blood glucose level at 60 min was not seen at the 12.5 and 6.25 mug/100 g body weight doses. Blood lactate concentrations did not show any significant variations by the injections of glucagon. In fasting rats, glucagon at the 100 mug/100 g body weight dose caused similar increase in blood FFA as that in fed ones. In fed cold-adapted rats at 5 degree C glucagon at the dose of 100 mug/100 g body weight brought about similar effects in elevation of blood FFA level and its time-course as those in fed rats adapted to 25 degree C. However, under fasting condition cold-adapted animals exhibited greater increment in blood FFA level at 5 min than those adapted to 25 degree C, while an elevation of blood FFA at 240 min was not observed in the former animals. These results indicate for the first time an in vivo lipolytic action of glucagon in rats and further suggest an enhanced sensitivity to lipolytic action of glucagon in cold adaptation.
Acclimatization↗
[Aldosterone radioimmunoassay kit without the use of chromatography].
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Aldosterone↗
Articular lesions in experimental Erysipelothrix insidiosa infection in rats.
Articular lesions were studied in the extremities and vertebral column in murine erysipelas infection. Pathologic alterations found in those different joint systems were essentially the same in character. In the early stage of infection, phlegmon-like inflammation was observed in the periarticular loose connective tissue. Abundant fine Gram-positive bacilli were free in inflamed edematous tissue. Then, active serofibrinous exudation and emigration of leukocytes occurred in the synovial membrane, articular cartilage, annulus fibrosus, and nucleus pulposus with the development of the disease. These exudative changes disappeared gradually. Instead of them, proliferation of synovial cells accompanied by dense infiltration with lymphocytes and plasma cells became conspicuous. At the same time, chondro- and osteoclastic activity occurred in the joints of the extremities or regions adjacent to the intervertebral disk. Capsular and subchondral pannus often resulted from an excessive proliferation of granulation tissue. In the late stage, they synovial membrane and granulation tissue underwent fibrosis, adhesion and ossification. Finally, these changes resulted in fibrous or bony ankylosis and deformation. Gram-positive bacilli were hardly detected in histological preparations derived from animals in the chronic stage when proliferative change was predominant in the articular lesions.
Animals↗