共查询到20条相似文献,搜索用时 15 毫秒
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Dichloroacetate (DCA) reduces blood glucose, lactate and lipids in diabetes or during fasting. Chronic use of DCA, however, is limited by toxicity, probably due in part to its rapid conversion to oxalate in vivo. In theory, therefore, DCA's efficacy may be retained and its toxicity minimized by controlling its rate of metabolism. We attempted to alter DCA pharmacokinetics and bioavailability by synthesizing various derivatives comprising DCA esters with polyols and DCA ionic complexes. Twenty-four hour fasted, nondiabetic rats received single, orogastric doses of saline (control) sodium DCA (100mg/kg) or the following derivatives (D1-4): the esters D1-D3: potassium tetra (dichloroacetyl) glucuronate (D1), inositol-monophosphate-tetradichloroacetate (D2), inositol-hexadichloroacetate (D3) and inositol-hexa [N-methylnicotinate] hexadichloroacetate salt (D4). Each derivative was administered at a dose that would ultimately provide 100 mg/kg DCA as the anion. All derivatives were orally effective in significantly decreasing blood glucose and lactate. D4 exerted the most potent and long-lasting glucose- and lactate-lowering effects, yet increased plasma DCA concentrations less than an equivalent dose of the sodium salt. When administered to reverse light-cycled rats, D4 markedly inhibited the incorporation of tritiated water into cholesterol and triglycerides. We conclude that derivatives of DCA retain the biological activity of the parent compound, but may exhibit different pharmacokinetics. They may eventually prove useful in the treatment of diabetes mellitus, hyperlipidemia and lactic acidosis in man. 相似文献
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Obestatin is purported to be a peptide hormone encoded in preproghrelin. We studied the metabolic effects of continuous infusion of obestatin via subcutaneously implanted osmotic mini-pumps. Administration of up to 500nmol/kg body weight/day obestatin did not change 24h cumulative food intake or body weight in rats. Similarly, no effects were observed when obestatin was infused at 1000nmol/kg body weight/day for seven days. This dose of obestatin infused during a 24h fast did not alter weight loss, suggesting that obestatin has no effect on energy expenditure, and this dose did not alter glucose or insulin responses during an IPGTT. Obestatin was originally proposed to interact with GPR39 and subsequently the receptor for GLP-1. While both receptors are expressed in pancreatic islets, incubation with obestatin did not alter insulin release from islets in vitro. Moreover, obestatin did not bind to INS-1 beta-cells or HEK cells overexpressing GLP-1 receptors or displace GLP-1 binding to these cells. Our findings do not support the concept that obestatin is a hormone with metabolic actions. 相似文献
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The effects of acute manganese (Mn) toxicity on tissue manganese concentrations and on plasma glucose levels were investigated in adult male Sprague-Dawley rats. Manganese injection in all tissues analyzed was reflected by a significant increase in Mn concentration that was transitory. Changes in the molecular localization of Mn in liver following injection include both increases in protein-bound Mn and low molecular weight Mn complexes. A rapid, dose-responsive rise in blood glucose followed Mn injection, whereas circulating insulin levels decreased after injection. These data show that acute changes in tissue Mn levels can have a pronounced effect on carbohydrate metabolism. 相似文献
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Liu G Hughes CL Mathur R Foster WG Davis VL Magoffin DA 《Reproduction, nutrition, development》2003,43(6):567-576
As an outgrowth of our interest in the potential toxicity of dietary galactose, we investigated the metabolic effects of high lactose diets in Long-Evans female rats. Seventy-five Long-Evans female rats (25-day-old) were randomized to receive one of 3 diets for 7 months: glucose diet (CON); low lactose diet (10.5%, LLD); or a high lactose diet (41.9%, HLD). Necropsy was performed seven months after randomization. HLD animals had significantly lower body weights than controls (P < 0.01). These animals continued to grow, however at a retarded rate compared to the CON group. The HLD group also had significantly lower triglyceride and non-esterified fatty acid levels than the CON group (P < 0.01 and P < 0.05). Serum glucose concentrations were lower in the HLD group compared to CON animals (P < 0.05), while serum insulin levels were lower than both the LLD and CON animals (P < 0.01 and P < 0.05). Leptin exhibited a similar trend. Thyroid studies revealed no difference in TSH between groups. Free T4 was significantly higher in HLD rats compared to LLD and CON rats while free T3 was lower in the HLD group (P < 0.05). This indicates a possible impairment in T4 to T3 conversion. Our data suggests that a long-term high lactose diet is associated with a decrease in insulin and leptin levels, and an increase in the insulin to glucose ratio. However, these changes are seen in the presence of a decreased body mass. A significant effect on thyroid hormone metabolism is also seen, and may be an adaptive mechanism in lactose-fed rats. 相似文献
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Z Etzion R Yagil 《Comparative biochemistry and physiology. A, Comparative physiology》1987,86(1):49-55
Research on laboratory rats confirmed that drinking sea-water when dehydrated, was not beneficial and caused impaired renal function. When the concentration of sea-water in the drinking water is gradually increased there is a gradual increase in water uptake and corresponding urine excretion. At 50% sea-water the maximum uptake and excretion is reached. Following this there is a decline in appetite, water uptake and urine secretion. When on 100% sea-water, the creatinine clearances were greater than on tap water, while urine/plasma osmolalities (U/P) averaged 7. The only higher U/P was found in animals drinking sea-water when dehydrated, i.e. a U/P of 11. The urea metabolism appears to be suited to either the need to conserve body water, up to 50% sea-water, or to guarantee an adequate urine production, from 50% sea-water to pure sea-water. It is suggested that when a man is stranded at sea it is not advisable to drink all the fresh water and then be compelled to drink sea-water when dehydrated. It is better to slowly increase the sea-water uptake. This will prolong the time before sea-water needs to be drunk and result in only minor metabolic changes. Return to fresh water will be followed by an immediate return to normal homeostasis. 相似文献
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The study is undertaken to determine the effect of adrenal corticosteroid depletion after adrenalectomy on carbohydrate, protein and fat metabolism as well as maturation and functional efficacy of the immunocompetent cells. Beside biochemical and hematological parameters, whether in vivo glucocorticoid depletion has any modulatory effects on splenic macrophage responses to bacterial challenge with regards to intracellular killing, nitric oxide release and cellular integrity, were determined. Major findings of our study indicate that blood glucose, urea and total inorganic phosphate levels showed a time dependent increase in adrenalectomized rats compared to control. Total glycogen content in liver was decreased gradually due to adrenal corticosteroid insufficiency. Hematological parameters like hemoglobin concentration, hematocrit value, total leukocyte count and differential count were also found to increase in the adrenalectomized group with respect to intact group. From the functional study of immunocompetent cells, intracellular killing capacity of splenic macrophages recovered from control and adrenalectomized rats after 10 and 20 days of adrenalectomy showed no significant alteration; however, the function of splenic macrophages recovered from rats after 30 days of adrenalectomy showed altered response. Nitric oxide released from splenic macrophages of adrenalectomized rats was less than that of control animal even after stimulation with lipopolysaccharide. DNA fragmentation assay showed a lesser degree of fragmentation of splenic macrophages obtained from adrenalectomized rats indicating, apoptotic death of cells in this group decreases. Adrenal corticosteroid insufficiency due to adrenalectomy interferes with metabolic and hematopoietic functions and modulates the development and maintenance of normal immunitary status, which in turn influences the inflammatory response. 相似文献
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Hormones associated with parturition prime rats to behave maternally, although hormonal changes are not necessary for these behaviors to occur. Experience with pups after birth enhances maternal responsiveness after a period of isolation, creating a maternal memory. The purpose of this study was to determine the role of corticosterone in the formation of maternal memory. Adrenalectomy or sham surgeries were performed in late gestation with corticosterone or vehicle pellets being given to adrenalectomized rats. Pups were removed immediately following parturition, and half of the rats received 4 h of pup experience, while the other half received only brief pup experience associated with parturition. Ten days following pup experience, foster pups were given to all rats. Latency to become maternal and maternal behaviors on the first 2 days of re-exposure and the first two maternal days were recorded. Among adrenalectomized rats given corticosterone, 4-h experience with pups decreased maternal latency when compared to brief experience with pups. This maternal experience effect was not found in comparisons between adrenalectomized rats not given corticosterone. In addition, corticosterone decreased latencies regardless of pup experience. Corticosterone also increased maternal behavior upon initial exposure to foster pups. In conclusion, corticosterone enhanced maternal memory and initial maternal behavior in postpartum rats. 相似文献
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Effects of acute administration of L-tryptophan (L-TRP. 250.0 mg/kg, i.p.) on active avoidance conditioning and "open-field" behavior were studied in male rats after adrenalectomy of dexamethasone administration. L-TRP inhibited the acquisition and reproduction of active avoidance reaction in adrenalectomized and dexamethasone-treated rats. Moreover, L-TRP decreased horizontal locomotor activity and grooming behavior in the "open field" on adrenalectomized rats. On the contrary, p-CPA restored the active avoidance conditioning in adrenalectomized rats and rats with excess of glucocorticoids. Also, p-CPA increased the total locomotor activity and grooming behavior in the "open field" in adrenalectomized rats, but decreased horizontal locomotor activity and enhanced emotional reaction in dexamethasone-treated rats in the "open field". 相似文献
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This study was undertaken to evaluate theeffects of regular endurance-type exercise on glucose tolerance andglucose-stimulated insulin response (GSIR) in ovariectomized (OVX) ratswith and without estrogen replacement. To do that, OVX Sprague-Dawleyrats were compared with an OVX estradiol-treated group (OVXE2) and asham-operated (Sham) group. Each of these groups was subdivided into asedentary and a treadmill-trained (8 wk) group. Intravenous glucosetolerance tests (0.5 g/kg) were conducted in all rats 48 h afterthe last training session. Plasma levels of 17-estradiol and theuterus weight were significantly (P < 0.05) lower inOVX compared with results in Sham and significantly (P < 0.01) higher in OVXE2 (hyperestrogenic) compared with results inSham. Body weights were significantly (P < 0.01)different among groups, in the following decreasing order: OVX, Sham,and OVXE2. The average daily food intake was significantly(P < 0.01) increased in OVX rats compared with Sham,whereas estradiol treatment diminished this effect (P < 0.01). Exercise training was found to alter none of theabove-mentioned variables in all three experimental conditions. Although the mean integrated area under the glucose and insulin curveswas not affected by OVX, training induced a significant (P < 0.01) reduction in the mean integrated area underthe insulin curve in all three experimental conditions. It is concludedthat the positive effects of physical training on improving GSIR in OVXand hyperestrogenic animals are similar to what has been found in Sham. 相似文献
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K Yamanouchi T W Stephens K Chikada S J Dominianni H Behforouz P Scislowski A DePaoli-Roach D W Allmann R A Harris 《Archives of biochemistry and biophysics》1992,294(2):609-615
Proglycosyn, a phenylacyl imidazolium compound that lowers blood glucose levels, was demonstrated previously to promote hepatic glycogen synthesis, stabilize hepatic glycogen stores, activate glycogen synthase, inactivate glycogen phosphorylase, and inhibit glycolysis. In the present study proglycosyn was found to inhibit fatty acid synthesis, stimulate fatty acid oxidation, and lower fructose 2,6-bisphosphate levels, but to have no significant effects on cell swelling and the levels of cAMP in hepatocytes prepared from fed rats. Verapamil and atropine blocked the effects of proglycosyn on glycogen metabolism, but these compounds inhibit proglycosyn accumulation by hepatocytes. Proglycosyn stimulated phosphoprotein phosphatase activity in postmitochondrial extracts, as measured by dephosphorylation of phosphorylase a and glycogen synthase D, but this action required a very high concentration of the compound, making it unlikely to be the actual mechanism involved. It is proposed that a metabolite of proglycosyn is responsible for its metabolic effects. 相似文献