Search PubMed⌕ Search

Biomedical subjects

T T Yen

Publications and source records attributed to T T Yen.

At least 37 records · Page 2Linked to original sources
PubMed1988

AL-1576, an aldose reductase inhibitor (ARI), did not prevent the decrease of norepinephrine turnover in diabetic rats.

ONO-2235 [(E)-3-carboxymethyl-5-[(2E)-2-methyl-3-phenyl-propenylidene]rhodanine], an ARI, was reported to prevent significantly the decrease of norepinephrine (NE) turnover in three tissues of streptozotocin (STZ)-diabetic rats (1). To examine whether the partial restoration of NE turnover by ONO-2235 is related to its ARI activity, the effect of another ARI, AL-1576 [spiro(2,7-difluoro-9H-fluoren-9, 4'-imidazoline)-2'5'-dione], on NE turnover in STZ rats was investigated. STZ caused an accumulation of sorbitol in the lens and decreased NE turnover in interscapular brown adipose tissue (IBAT), heart and pancreas. AL-1576 totally prevented the accumulation of sorbitol in the lens but had no effect on the decreased NE turnover in all three tissues. These results suggest that the partial prevention of NE turnover decrease by ONO-2235 may not have been mediated by its ARI activity.

Aldehyde Reductase↗
PubMed1987

MTP-1307, a novel antidiabetic agent, improves the glucose intolerance of viable yellow obese-diabetic mice.

MTP-1307 is an oral antidiabetic agent with a unique profile. It improves the glucose intolerance of viable yellow obese-diabetic mice at 25 mg/kg whereas at 300 mg/kg, it only marginally lowers the basal glucose levels of the same mice. This selective activity on exogenous glucose makes MTP-1307 potentially a useful agent to treat postprandial glucose intolerance without causing hypoglycemia.

Animals↗
PubMed1984

Thermogenesis and weight control.

Compound LY104119, [R-(R*,S*)]-4-[3-[(2-hydroxy-2-phenylethyl)amino]butyl]benzamide monohydrochloride, was found to be a potent beta-agonist in the mouse. Its Ki for displacing the binding of (-)-3H-dihydroalprenolol to beta-receptors on the lung membranes from either viable yellow obese mice (VY/WfL-Avy/a) or their corresponding normal controls (VY/WfL-a/a) was 3 X 10(-7) M, comparable to that of isoproterenol which was 2 X 10(-7) M. LY104119 increased the concentration of cyclic AMP in adipose tissue, stimulated lipolysis in vitro and in vivo and the expiration of CO2 in vivo. When given s.c. or p.o., LY104119 reduced the body weight of Avy/a mice without altering the food consumption. The loss of triacylglycerol accounted for a major portion of the weight loss and the weight was recovered after the treatment was withdrawn. When fed in the diet, LY104119 reduced the weight of Avy/a mice and caused a moderate increase of food intake. Thermogenesis (whole body heat production) of the treated mice increased. An elevated level of hepatic glucokinase activity regularly found in these mice was almost normalized to the level measured in normal mice. The kinetic properties of the beta-receptors were not altered, but the number of beta-receptors on lung membranes was reduced about 25 percent. The lipolytic response of epididymal adipose tissue to LY104119 or isoproterenol, however, was not changed. When slightly overweight a/a mice were treated with LY104119 in the diet, they lost weight, but a similar treatment of normal-weight a/a mice caused a loss of only a small amount of carcass triacylglycerol without affecting the body weight. These normal-weight a/a mice were able to maintain their weight by an exorbitant increase of food intake. When this large increase of food consumption was not allowed, ie by being restricted to normal amounts of food intake, normal-weight a/a mice fed LY104119 did lose weight. Thermogenesis increased in all LY104119-treated a/a mice. However, the increase in the LY104119-treated but diet-restricted a/a mice was smaller than that in the LY104119-treated a/a mice fed ad libitum. We conclude from these observations that: Compound LY104119 was able to decrease weight in Avy/a mice apparently through the stimulation of the beta-adrenergic system. The metabolic responses to LY104119 were not different in obese Avy/a mice and normal a/a mice. The difference between the Avy/a mice and the a/a mice was in their ability to increase their food consumption to compensate for the energy loss caused by LY104119.

2-Hydroxyphenethylamine↗
PubMed1984

The antiobesity and metabolic activities of LY79771 in obese and normal mice.

Without affecting the appetite, Compound LY79771 reduced the body weight of obese Avy/a mice, prevented young Avy/a mice from becoming obese and ob/ob mice from becoming overtly obese. This weight-controlling effect of LY79771 was reversible upon withdrawal of treatment. The major portion of the weight change induced by the compound was due to a reduction in triacylglycerol content of the body. Hyperinsulinemia and hyperglycemia of the obese mice were also improved. In spite of its potent lipolytic activity, only a 20 to 25 per cent excess of fatty acid was found in the liver after dosing. No accumulation of fatty acid was observed in the carcass. A single dose of LY79771 also stimulated metabolism as indicated by the increase of CO2 expiration. The transient rise of body temperature that occurred after each injection in a long-term treatment regimen suggested that the compound was thermogenic. LY79771 had no effect on the weight of normal mice.

2-Hydroxyphenethylamine↗
PubMed1983

Stimulation of cyclic AMP and lipolysis in adipose tissue of normal and obese Avy/a mice by LY79771, a phenethanolamine, and stereoisomers.

The stimulation of cyclic AMP and lipolysis by LY79771, a phenethanolamine antiobesity compound, and its 3 stereoisomers in adipose tissue of obese viable yellow mice and normal mice were studied. Both activities were stereo-specific with LY79771, the R,S isomer, and LY79730, the R,R isomer, being more potent than LY103085, the S,S isomer, and LY103672, the S,R isomer. Propranolol, a nonspecific beta-antagonist, completely inhibited the elevation of cyclic AMP and lipolysis whereas atenolol, a specific beta 1 antagonist, inhibited the elevation of cyclic AMP but did not completely inhibit lipolysis. These findings indicate that the elevation of cyclic AMP was mediated by the beta 1-receptor whereas the stimulation of lipolysis was mediated by both the beta 1 and beta 2 receptors. The adipose tissue of the obese viable yellow mice responded to these compounds less than that of the normal mice.

2-Hydroxyphenethylamine↗
PubMed1982

The selectivity of the anorectic effect of satietin. IV. The ineffectiveness of satietin on the sexual performance of male CFY rats.

Satietin a recently discovered potent endogenous anorectic agent was claimed to be a highly selective anorectic substance, devoid of any effect on other behavioral system. In the copulator male rats, in contrast to amphetamine, fenfluramine and fluoxetine it failed to influence the mating activity. This finding further supports the view that satietin has highly selective effect on feeding behavior.

Amphetamine↗
PubMed1981

Constitutive hepatic glucokinase activity in db/db and ob/ob mice.

The specific activity of hepatic glucokinase (ATP: D-glucose 6-phosphotransferase, EC 2.7.1.2) in db/db mice and ob/ob mice was higher than in normal mice. All enzymes had a similar Km and, thus, the difference in activity was not due to differences in the affinity of enzyme molecules to substrates. Mixing liver extracts with high or low enzyme activities yielded additive results, as expected, which ruled out the involvement of an inhibitor or activator of the enzyme. Fasting normal mice of either strain for three days decreased glucokinase activity. However, fasting db/db or ob/ob mice for as long as 10 days had no effect on enzyme activity, indicating that glucokinase in db/db or ob/ob mice was out of regulation or constitutive. The constant, abnormally high glucokinase activity may be a contributing factor to the obesity of ob/or or db/db mice. These mice provide a model system to study the regulation of this rate-limiting enzyme of glucose metabolism.

Animals↗
PubMed1981

Lowering of blood pressure by direct- and indirect-acting serotonin agonists in spontaneously hypertensive rats.

1-(m-Trifluoromethylphenyl)piperazine, a serotonin agonist, lowered blood pressure in spontaneously hypertensive rats (SHR) at doses of 2 to 10 mg/kg s.c. A structurally related compound lacking serotonin agonist activity, 4-(m-trifluoromethylphenyl)piperidine, was ineffective. Quipazine, another serotonin agonist, lowered blood pressure in SHR at doses of 0.1 to 2 mg/kg s.c. Fenfluramine, a serotonin-releasing drug, lowered blood pressure in SHR at doses of 2 and 5 mg/kg s.c. Metergoline (3 mg/kg s.c.), a serotonin antagonist, elevated blood pressure and prevented the decrease by all of the above agents. These findings are consistent with the view that enhancement of central serotonergic function lowers blood pressure in SHR.

Animals↗
PubMed1980

Synthesis and blood pressure lowering activity of 3-(substituted-amino)-1,2,4-benzothiadiazine 1-oxide derivatives.

A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimethoxy-1-methyl-1H-1,2,4-benzothiadiazine 1-oxide hydrochloride. This compound in animal tests was equipotent to the known antihypertensive Prazosin.

Animals↗
PubMed1980

Hepatic insensitivity to glucagon in ob/ob mice.

Hepatic cAMP concentration of normal mice increased 40 fold within 10 min after a single dose of glucagon (2 mg/kg, IP). In contrast, hepatic cAMP increased only 2 fold in ob/ob mice. Glucagon induced hepatic L-phenylalanine:pyruvate aminotransferase and stimulated glycogenolysis in normal mice but failed to elicit these cAMP-mediated responses in ob/ob mice. The insensitivity of ob/ob mice to glucagon was not ameliorated by fasting or by theophylline.

Animals↗
PubMed1979

Nylidrin: a potent anti-hypertensive agent in hypertensive rats.

Nylidrin HCl lowered the blood pressure and increased the heart rate of conscious, spontaneously hypertensive rats (SHR), Goldblatt hypertensive rats, and DOCA hypertensive rates. In SHR, the minimum effective dose was 0.5 mg/kg, s.c. At that dose, the anti-hypertensive activity of nylidrin lasted more than 3 hours. Propranolol reversed both effects on blood pressure and heart rate by nylidrin, whereas atenolol, a specific cardiac beta 1 blocker, only blocked or reversed the tachycardia caused by nylidrin but did not block the anti-hypertensive effect of the compound. In normotensive rats of Wistar/Kyoto strain (WKY) and Holtzman strain, nylidrin at 5 or 10 mg/kg, s.c., produced a transient hypotensive effect which lasted less than an hour and tachycardia that persisted for several hours. In WKY, atenolol prolonged the hypotensive activity of the compound by partially reversing the tachycardia. These observations indicate that SHR is more sensitive than WKY to the anti-hypertensive activity of nylidrin, which is probably caused by vasodilatation mediated by beta 2 receptors.

Animals↗
PubMed1978

Control of obesity in Avy/a mice by 5alpha-androstan-17-one.

Treating VY/WfL-Avy/a mice with 5 alpha-androston-17-one, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented the mice from becoming obese. The weight difference between treated and control Avy/a mice was mainly due to a decreased accumulation of triacylglycerol. The compound did not suppress appetite, had no detectable toxicity and did not affect the lipogenesis rates in the liver and carcass. The weight-controlling effect of 5alpha-androstan-17-one in Avy/a mice was reversible upon withdrawal of treatment.

17-Ketosteroids↗