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Biomedical subjects

K Shimakawa

Publications and source records attributed to K Shimakawa.

33 records · Page 2Linked to original sources
PubMed1986

The antiobesity action of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124).

The antiobesity effects of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124) were examined in rats and dogs. AO-124 suppressed food intake dose dependently in normal, Zucker fatty and VMH-obese rats, and beagle dogs. Its anorectic activity was not altered by pretreatment with methysergide, a serotonin receptor blocker. AO-124 also reduced the hyperphagia induced by 2-deoxy-D-glucose but not that induced by insulin, noradrenaline or muscimol, suggesting that the anoretic mechanism of AO-124 may be implicated in a glucostatic regulatory system of feeding. In addition, AO-124 decreased insulin secretion in response to an oral, but not an intravenous, glucose load. Such a suppression in insulin secretion may be explained by slow absorption of glucose from the intestine: AO-124 delayed the gastric emptying time of glucose and inhibited the active transport of glucose as observed in the everted small intestine. Two week administration of AO-124 to Zucker fatty rats resulted in a significant reduction of plasma insulin levels, body weight gain, and body lipid without exerting any changes in body protein. These findings indicate that AO-124 may be useful as an antibesity agent on the basis of its unique mechanisms of action.

Animals↗
PubMed1984

Relation of body energetic status to dietary self-selection in Sprague-Dawley rats.

Self-selection from carbohydrate, protein and fat sources including essential micronutrients was studied in male Sprague-Dawley rats that were 4 weeks of age at the beginning of the experiment. During the experimental period of 14 days, the intake of carbohydrate and fat was quite constant, whereas that of protein increased gradually. The mean intake of carbohydrate, protein, and fat was 31.1 +/- 3.5%, 56.1 +/- 4.6%, and 12.8 +/- 2.8% of the total energy intake, respectively. Animals fed on a mixed diet consisting of high sucrose, consumed 65.1% of their daily energy as carbohydrate, 17.6% as protein, and 17.3% as fat. Total energy intake and body weight gain were not significantly different between the rats on self-selection and those fed on the mixed diet. These results indicate that young rats on dietary self-selection were able to gain body weight comparable to that of rats fed on the mixed diet. Body energetic status affected self-selection patterns. In rats fasted for 5 days or fed on a protein-free diet for 21 days, fat intake increased, but protein intake decreased. On the other hand, fat intake decreased in animals given a sucrose diet higher in energy content than the stock diet; these animals exhibited increased accumulation of body energy. These results indicate that dietary self-selection is closely related to nutritional and physiological body requirements.

Animals↗
PubMed1984

Feeding in response to insulin and 2-deoxy-D-glucose in Zucker rats on dietary self-selection.

Adult male fatty and lean rats of Zucker strain were given access ad libitum to either a single nutritionally complete diet, or a self-selection regime with separate sources of three macronutrients, protein (casein), fat (hydrogenated coconut oil), and carbohydrate (sucrose). Animals on the single diet were fed on a powdered stock diet, and then switched to the self-selection regime. Energy intake on the self-selection regime was the same as that for the single diet condition in both fatty and lean rats. Fatty rats consumed 45% more energy than did their lean littermates. Further, fatty rats selected 47.0% of their total calories as protein, 30.1% as fat, and 22.9% as carbohydrate. The respective percentages for lean rats were 56.1, 13.0 and 30.9. In lean rats, the injection of insulin (10 U/kg) or 2-deoxy-D-glucose (500 mg/kg, 2DG) failed to increase energy intake, but increased carbohydrate intake 2 times by attenuating protein intake. Also in fatty rats, insulin did not increase energy intake, but it did increase carbohydrate by 50% by attenuating fat intake. 2DG decreased energy intake by attenuating carbohydrate and fat intakes in fatty rats. Fatty rats were slightly less hypoglycemic to insulin, but more hyperglycemic to 2DG than lean rats. These different self-selection patterns of fatty rats seemed to be associated with their endocrine, metabolic, and behavioral abnormalities.

Animals↗
PubMed1983

Recovery from impairment in feeding response to glucoprivic stimuli and in sensitivity to diabetogenic agents in riboflavin-repleted rats.

Male weanling rats, fed a riboflavin-deficient diet for 14 days showed impairments in reactivity to the hyperphagic action of either insulin or 2-deoxy-D-glucose (2DG) and in sensitivity to the diabetogenic action of streptozotocin or alloxan. The intraperitoneal injection of riboflavin (160 micrograms/rat) resulted in an immediate restoration in FAD-dependent activation of erythrocyte glutathione reductase and in the reactivity of food intake to insulin, whereas the reactivity of food intake to 2DG was restored after 3 days of riboflavin repletion. The sensitivity to diabetogenic agents was not restored solely by the riboflavin injection but required 3 hours of feeding as well. These findings indicate that the riboflavin deficiency caused some defects at specific glucosensitive sites localized in the pancreas and the brain and that some metabolic processes were necessary to restore the sensitivity.

Alloxan↗
PubMed1982

Reduced sodium excretory ability in young spontaneously hypertensive rats.

The excretory response of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) to acute saline load was compared to that of control Wistar Kyoto rats (WKY) in pre- and early-hypertensive phases. In each of the 3 groups, half of the animals was fed a low salt diet, and the other half a normal diet. At the prehypertensive phase, sodium and water excretion and sodium-potassium ratio in the urine in SHR and SHRSP fed a normal diet were significantly less than those in WKY. The ability of SHR to excrete sodium and water, however, was improved by the elevation of blood pressure that developed between 7 and 10 weeks after their birth. While young SHR fed a normal diet had a reduced ability to excrete sodium, the young SHR fed a sodium-restricted diet did not. Salt restriction significantly delayed the appearance of high blood pressure in both SHR and SHRSP. These results suggest that in both SHR and SHRSP, and elevation of blood pressure is important to compensate for the reduced ability to excrete sodium and water.

Animals↗
PubMed1979

Studies on analgesic agents. 1.1a Preparation of 1,2-diphenyl-2-(4-substituted 1-piperazinyl)ethanol derivatives and structure-activity relationships.

The preparation and analgesic activity of a series of the title compounds (8-55 and 57) are described. The intermediates, 2-phenyl-2-(1-piperazinyl)acetophenones 5 and 6, were prepared from benzyl phenyl ketones 3 via their bromides 4. On reduction, compounds 5 afforded the titled compounds 8-12, 16, and 26-48. Compounds 13-15 and 17-25 were obtained by alkylation or benzylation of 1.2-diphenyl-2-(1-piperazinyl)ethanols 7 derived from 6 by reduction. The reduction of 5 and 6 with metal hydrides predominantly gave the erythro isomers. The erythro isomers were remarkably more active than their threo isomers. The more active members in this series of compounds were 16 and derivatives 35 and 37-44 of dl-erythro-1-phenyl-2-(substituted phenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl]ethanol. Compounds 16, 43, and 44 were the most active with a potency of about two to three times that of codeine. Racemates 16 and 38 were resolved into their optical isomers and it was found that (-)-16 and (+)-38 were more potent than their antipodes. Structure-activity relationship are discussed.

Analgesics↗
PubMed1975

Effects of nutritional factors on the development of ethanol-induced fatty liver in KK and KK-Ay mice.

KK and KK-Ay mice developed a steady and reproducible fatty liver when they were given free access to an ethanol solution as a drinking fluid for 10 to 20 days. The present studies were undertaken to elucidate effects of nutritional factors on liver fat contents of the mice given water or ethanol solution. In contrast to cornstarch, sucrose tended to increase the liver fat of control mice. A higher concentration of dietary casein lowered the liver fat of control mice, whereas the dietary concentration of cottonseed oil did not significantly affect the liver rat levels either in control or ethanol groups. Thus the standard basal diets favorable for the development of the alcoholic fatty liver have been established, for example, 10% cottonseed oil, 25 and 30% casein, 58.4 and 53.4% cornstarch for KK (12-15 weeds old) and KK-Ay (5-10 weeks old), respectively. Neither choline, myoinositol, nor any lipotropic agent tested prevented the development of the alcoholic fatty liver. Unlike in rats, orotic acid did not induce a fatty liver but rather alleviated the ethanol-induced fatty liver in these mice.

Age Factors↗
PubMedDate not supplied

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Aging↗