Alterations of lipid and cholesterol metabolism in cachectic tumor-bearing rats are prevented by insulin

The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive body weight loss, associated with reduced food intake, and protein and lipid hypercatabolism. Because insulin regulates glucose as well as lipid and protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus insulin (107 micromol. kg body wt-1. d-1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4), pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells ( approximately 10(8) cells/rat) were inoculated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The metabolism of both cholesterol and lipids was investigated in tumor cells, and ascitic fluid and blood serum were investigated at the end of treatment. Insulin prevented the reduction of food intake (19 +/- 0.6 vs. 13 +/- 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with insulin, respectively), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P < 0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1 mmol/L, P < 0.01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P < 0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240 +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mmol/L, P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated by 14C-acetate incorporation into cholesterol, in both liver (3,337 +/- 245 vs. 830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,693 vs. 4,196 +/- 527 Bq/10(6) cells, P < 0.01). Thus insulin treatment ameliorated many metabolic derangements, with a lengthening of rats survival time (7 +/- 1 vs. 11 +/- 1 d, P < 0.05) without significantly stimulating tumor growth. These data, together with our previous observations on the effectiveness of insulin on protein turnover perturbations, suggest that many metabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone.     

不平衡支链氨基酸对化疗荷瘤大鼠营养及生存状况的影响

目的:观察不平衡支链氨基酸疗法联合氟尿嘧啶(5-FU)对荷瘤大鼠营养及生存状况的影响.方法:SD大鼠空肠造口,皮下接种Walker-256癌肉瘤,分为A(平衡氨基酸 等渗盐水)组、B(平衡氨基酸 5-FU)组、C(去缬氨酸 5-FU)组、D(去缬氨酸及增加亮氨酸 5-FU)组.测定各组治疗后体重的变化、主要脏器的重量、血清前清蛋白(PA)和转铁蛋白(TF)浓度,并观察荷瘤大鼠的生存时间.结果:C组与A、B组相比较,体重丢失明显增加(P＜0.05或P＜0.01),两肾和左侧腓肠肌的相对重量、血清PA和TF浓度明显降低(P＜0.05或P＜0.01);D组与C组比较,体重丢失明显减少(P＜0.01),两肾和左侧腓肠肌的对相重量、血清PA和TF浓度明显升高(P＜0.05或P＜0.01);A组宿主生存时间最短,D组与A、B、C组比较,生存时间明显延长(P＜0.01).结论:去缬氨酸肠内营养和5-FU对荷瘤宿主营养状况产生不利影响,而在肠内营养中增加亮氨酸浓度能改善前两者引起的宿主营养不良.去缬氨酸及增加亮氨酸肠内营养联合5-FU化疗能明显延长宿主的生存时间.     

不平衡氨基酸对肿瘤生长的影响

目的 比较几种不平衡氨基酸营养支持对肿瘤生长的影响。方法 荷Walker-256癌肉瘤SD大鼠,空肠喂饲肠外营养制剂10天,据所喂饲制剂中氨基酸组成的不同,分为：A组（平衡氨基酸组）、B组（增量精氨酸不平衡氨基酸组）、C组（去蛋氨酸不平衡氨基酸组）、D组（去缬氨酸不平衡氨基酸组）、E组（增量精氨酸、去蛋氨酸、去缬氨酸不平衡氨基酸组）。肿瘤体积增长速度、肿瘤重量、肿瘤重量／尸重,肿瘤组织PCNA指数,肿瘤细胞周期各时相百分比以及DNA倍性作为观察肿瘤生长速度的指标。结果 上述各指标值显示：B、C、D组与A组相比,除DNA倍性外,其余各项指标值均降低（P＜0．01）,但B、C、D组间比较无显性差异（P＞0．05）。E组与B、C、D组相比较,所有指标值均显降低（P＜0．05）。结论 平衡氨基酸促进肿瘤生长;增量精氨酸、去蛋氨酸、去缬氨酸三种不平衡氨基酸对肿瘤生长有同等抑制作用;增量精氨酸、去蛋氨酸、去缬氨酸复合不平衡氨基酸对肿瘤生长抑制作用更显。     

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats

The effect of glutamine (GLN)-supplemented total parenteral nutrition (TPN) on tumor growth and protein metabolism was investigated in tumor-bearing rats. Six days after implantation of AH109A hepatoma, rats received isonitrogenous TPN without or with alanyl-glutamine (25% of total N) for a period of 6 days. Protein turnover was assessed by continuous infusion of l4C-leucine and levels of GLN and glutathione were determined in muscle, jejunum and liver. Diet had no effect on tumor parameters: weight (mean = 4.4 g), GLN and glutathione concentrations, protein synthesis rate and bromodeoxyuridine-labeling index. Body weight loss was less pronounced in the GLN group (-5.5 +/- 1.2 vs. -9.4 +/- 1.4 g/5d). Decrease in plasma and muscle GLN concentrations (-30% and -17% vs. healthy controls, respectively) was limited in tumor-bearing rats receiving GLN-enriched TPN (-15% and +3%). GLN-supplemented TPN increased muscle and jejunum fractional synthesis rates (36% and 25% vs. standard TPN, respectively) and reduced body protein breakdown in tumor-bearing animals (303 +/- 33 vs. 421 +/- 66 mumol Leu/Kg/h). Decrease in jejunum glutathione levels was partially abolished in the GLN group: -50% vs. -64% in the standard TPN group; no effect was noticed in other tissues. The authors conclude that GLN-supplemented TPN improves protein metabolism at both the whole body and the tissue level, and prevents GLN and glutathione deficiencies associated with tumor implantation.     

不平衡氨基酸对肿瘤生长的影响

目的：比较几种不平衡氨基酸营养支持对肿瘤生长的影响。方法：荷Walker-256癌肉瘤SD大鼠，空肠喂饲营养制剂10天，根据所喂饲制剂中氨基酸组成的不同，分为A组（平衡氨基酸组）B组（增量精氨酸不平衡氨基酸组）、C组（去甲硫氨酸不平衡氨基酸组）、D组（去缬氨酸不平衡氨基酸组）、C组（增量精氨酸、去甲硫氨酸和缬氨酸不平衡氨基酸组）。以肿瘤体积增长速度，肿瘤重量，肿瘤重量／尸重，肿瘤组织PCNA指数，肿瘤细胞周期各时相百分比，以及DNA倍性作为观察肿瘤生长速度的指标。结果：上述各指标值显示：B、C、D组与A组相比，除DNA倍性外，其余各指标值均非常显著降低，但B、C、D组间比较无显著差异。E组与B、C、D组相比较，所有指标值均显著降低。结认：平衡氨基酸促进肿瘤生长；量精氨酸、去甲硫氨酸和去缬氨酸三种平衡氨基酸对肿瘤生长有不同等抑制作用；增量精氨酸，去甲硫氨酸和去缬氨氨酸复合不平衡氨基酸对肿瘤生长抑制作用更显著。     

Interleukin-1beta system in anorectic catabolic tumor-bearing rats

PURPOSE OF REVIEW: The onset of cancer anorexia and the accompanying neurological symptoms and signs involve the general influence of cytokines on the brain. Using methylcholanthrene to induce tumors in Fischer 344 rats, we measured various specific components of the cytokine-induced anorectic reaction, including: (1) IL-1beta system components (ligand, signaling receptor, receptor accessory proteins, and receptor antagonist); (2) TNF-alpha; (3) TGF-beta1; and (4) IFN-gamma in the tumor tissue, the liver and the brain. RECENT FINDINGS: The data show that IL-1beta, TNF-alpha and IFN-gamma messenger RNA were detected in the tumor tissue of anorectic tumor-bearing rats. In brain regions, anorexia is associated with the upregulation of IL-1beta and its receptor mRNA. All other mRNA remained unchanged in the brain regions examined. SUMMARY: This suggests that IL-1beta and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.     

Nutritional responses of tumor-bearing rats to oral or intravenous feeding

Two experiments were conducted with male rats weighing 170 to 190 grams. In experiment 1, some nutritional parameters were determined in tumor-bearing (TB) (Walker 256 carcinosarcoma) rats fed a 23.6% casein diet for 4 weeks after the tumor inoculation. Cumulative weight gain and food intake were less in TB rats than in nontumor-bearing (NTB) rats. At 3 and 4 weeks after the tumor inoculation, plasma histidine, alanine, and glycine levels were higher in TB rats than in NTB animals. The arginine level was lower in the plasma of TB rats at 4 weeks after the inoculation. The significance of decrease in plasma arginine with regard to tumor growth is discussed. In experiment 2, the effects of total parenteral nutrition (TPN) on TB rats were evaluated as compared with those of 5% glucose (Glc) solution. Body weights of TPN rats were maintained and their nitrogen (N) balances were positive during a 7-day experimental period, while 5% Glc animals showed severe body weight loss and apparent negative N balance. After the end of infusion, the plasma urea level of the TPN group was within normal range, whereas that of 5% Glc group showed a markedly high value. The plasma albumin level was higher in the TPN group. Liver and spleen weights were increased in TPN rats. Absolute tumor weight was somewhat greater in TPN rats than in 5% Glc rats, but the difference in tumor weight:body weight ratios became more slight. These results indicate that TPN was effective for maintaining the nutritional status of TB host without significant acceleration in tumor growth.     

六黄合剂对胰岛素抵抗大鼠胰岛素敏感性影响

目的 探讨中药复方六黄合剂对胰岛素抵抗大鼠胰岛素敏感性的影响。方法 应用地塞米松致大鼠胰岛素抵抗模型,观察六黄合剂对大鼠血糖、血清胰岛素水平和胰岛素敏感指数的影响。结果 六黄合剂能够降低胰岛素抵抗大鼠口服葡萄糖耐量试验后2 h血糖浓度(2 hBG)和空腹血清胰岛素水平(FINS),提高胰岛素敏感指数(ISI)(P<0.01)。结论 中药复方六黄合剂能够增强胰岛素抵抗大鼠胰岛素敏感性。     

Beta-hydoxy-beta-methylbutyrate supplementation affects Walker 256 tumor-bearing rats in a time-dependent manner

BACKGROUND & AIMS: Cancer cachexia affects intermediary metabolism with intense and general catabolism. Walker 256 tumor is a model injected either subcutaneously (Sc) or intraperitoneally (Ip), with different metabolic features. Beta-hydroxy beta-methylbutyrate (HMbeta) is a leucine metabolite with anti-catabolic properties, the aim of this study being to investigate its effects on metabolic parameters in both tumor models. METHODS: Controls (subcutaneous control group (ScC) and intraperitoneal control group (IpC)) and supplemented animals (subcutaneous supplemented group (ScS) and intraperitoneal supplemented group (IpS)) showed these results. RESULTS: Protein Sc values were (47.8%) lower than Ip groups. Sc group fat content was (65.16%) higher than Ip groups. Liver glycogen value for Sc groups was (38.4%) higher than Ip groups. Muscle glycogen value for Sc groups were (2.75 times) higher than Ip groups. Corticosterone and insulin values were lower (44.53%) and higher (45.94%), respectively, in Sc when compared with Ip groups. Glucose and lactate values for ScS were the lowest (61.7% and 41.53%) compared to other groups. ScC glutamine value was the highest (40.8%) of all groups. Glutamate Sc values were (42.65%) lower than Ip groups. Sc groups showed greater survival time compared with Ip groups. ScS group showed 100% increase in survival time when compared with ScC. CONCLUSIONS: HMbeta supplementation can increase survival time and promotes metabolic changes in cancer-bearing animals, but it seems to work in a time-dependent manner.     

Continuous intravenous infusion of ghrelin does not stimulate feeding in tumor-bearing rats

The development of anorexia continues to be a serious treatment issue for cancer patients. Because the orexigenic peptide, ghrelin, is active through systemic routes and activates hypothalamic neuropeptide systems known to be refractory in anorectic tumor-bearing (TB) rats, we investigated whether it would prevent the development of cancer anorexia when infused continuously intravenously. The 24-h food intake was increased in nontumor-bearing (NTB) rats at a dose of 288 microg/day ghrelin. However, no tested dose of ghrelin, up to 576 microg/day, elicited increased feeding in TB rats prior to or subsequent to the development of anorexia. In hypothalamus, ghrelin-infused TB rats exhibited significantly increased concentration of neuropeptide Y (NPY) as compared to saline-infused TB rats. Hypothalamic expression of NPY and agouti-related protein (AgRP) messenger RNA were elevated in ghrelin-infused TB rats as compared to NTB rats, but saline-infused TB rats also exhibited increased expression of AgRP. Proopiomelanocortin message was reduced in ghrelin-infused and saline-infused TB rats as compared to noninfused TB control rats. Although ghrelin infusion did not preserve muscle protein, a significant saving in body fat was observed in TB rats. Thus, the adiposity effects of ghrelin did not require an orexigenic response to the peptide. These results suggest that continuous ghrelin infusion may not be an effective treatment for cancer anorexia.     

镉对大鼠胰岛素水平的影响

目的研究镉对机体胰岛素水平的影响。方法采用随机区组方法,96只SD大鼠给予不同剂量的镉(CdCl20、50、100和200mgL),饮水染毒30天、60天、90天。测定不同染毒时间大鼠血胰岛素、血液、尿液中镉含量的改变以及肝、肾和胰脏中镉含量的改变。结果染毒组大鼠在染毒30天中、高剂量组和染毒60天的中剂量组血清胰岛素水平显著降低。各剂量组大鼠血、尿和胰脏中镉含量有显著增加。但胰脏中镉含量低于肾脏和肝脏。结论镉可以在胰脏组织蓄积,引起胰岛素水平降低。     

Impact of housing on the survival of persons with AIDS

Background  

Homeless persons with HIV/AIDS have greater morbidity and mortality, more hospitalizations, less use of antiretroviral therapy, and worse medication adherence than HIV-infected persons who are stably housed. We examined the effect of homelessness on the mortality of persons with AIDS and measured the effect of supportive housing on AIDS survival.     

Clenbuterol treatment increases muscle mass and protein content of tumor-bearing rats maintained on total parenteral nutrition

Treatment of tumor-bearing (TB) and control rats with the anabolic beta-2 agonist drug clenbuterol (CLE) for 14 days reduced food intake for 4 days initially. Feeding was increased in anorectic TB rats, however, during the last 7 days of drug administration. Since minimal muscle savings were observed in chow-fed TB rats treated with CLE, the anabolic effects of this drug were investigated in a second experiment on TB rats maintained on total parenteral nutrition (TPN). Sixteen days after the subcutaneous transplantation of methylcholanthrene-induced sarcomas rats was begun on a 2-week schedule of TPN. One group of these rats was treated daily for 14 days with CLE, while the remaining rats received injections of saline. Additional groups of TB and nonTB rats were maintained on rat chow for this period and treated with saline. Although TB rats maintained on rat chow or TPN and treated with saline exhibited significantly decreased gastrocnemius muscle weight and protein content, treatment of TB-TPN rats with clenbuterol normalized muscle mass and increased muscle protein content significantly and increased plasma concentrations of branched-chain amino acids. These results indicate that although nutritional support of TB organisms does not result in protein repletion, the addition of an anabolic drug renders the nutritional support highly efficacious.     

Elevated blood lactate is not a primary cause of anorexia in tumor-bearing rats

Tumor-bearing (TB) rats exhibit elevated concentrations of lactate in blood contiguous with the development of anorexia. Continuous intravenous infusion of lactate into non-TB rats reduced food intake at plasma concentrations lower than those observed in anorectic TB rats. Levels of neuropeptide Y (NPY) were elevated in the ventromedial (VMH) and dorsomedial hypothalamic regions of lactate-infused rats. The addition of the enhancer of pyruvate dehydrogenase activity, dichloroacetate (DCA), to the drinking water of TB rats (0.1-0.4%) normalized blood lactate concentration but had no significant effect on anorexia. However, the elevated concentration of NPY in the VMH of anorectic TB rats was also normalized by the DCA treatment. No alterations in regional hypothalamic levels of corticotropin-releasing factor were observed within any treatment conditions. These results suggest that, although hyperlactatemia may be involved in maintaining elevated NPY concentrations in anorectic TB rats, it does not appear to be a significant factor in the etiology of experimental cancer anorexia.     

吲哚美辛对癌性恶病质小鼠肌肉泛素-蛋白质酶途径的影响

目的:研究泛素-蛋白质酶途径在癌性恶病质小鼠骨骼肌中的表达以及吲哚美辛(IND)对其的调控作用. 方法:利用鼠结肠癌26细胞株皮下接种BALB/c小鼠,建立癌性恶病质模型.将30只BALB/c小鼠随机分为五组:对照组、荷瘤 等渗盐水组、荷瘤 IND 0.25 mg/(kg·d)组、荷瘤 IND 0.5 mg/(kg·d )组、荷瘤 IND 2.0 mg/(kg·d)组.监测各组小鼠去瘤体重和腓肠肌重量;测量血清TNF-α和IL-6水平,体外腓肠肌肌蛋白降解速率以及泛素-蛋白质酶途径组分mRNA表达. 结果:恶病质小鼠去瘤体重和腓肠肌重量明显下降(P< 0.01),血清TNF-α和IL-6水平明显升高(P< 0.01),腓肠肌蛋白质降解速率以及泛素蛋白质酶组分mRNA表达,均明显升高(P< 0.01).IND 0.5 mg/(kg·d)可以明显缓解恶病质小鼠腓肠肌重量的下降(P< 0.01),降低血清TNF-α(P< 0.05)和IL-6水平(P< 0.01),抑制体外腓肠肌蛋白的降解以及泛素蛋白质酶组分mRNA表达(P<0.01). 结论:泛素-蛋白质酶途径在癌性恶病质的骨骼肌消耗中起重要作用,它受炎性细胞因子调控.适当剂量的IND可能通过减少炎性细胞因子产生,抑制泛素-蛋白质酶途径的激活,缓解肌蛋白的降解.     

复配式粗杂粮对胰岛素抵抗大鼠LCN-2表达影响

目的 探讨全谷豆复配式粗杂粮对高脂膳食诱导胰岛素抵抗大鼠肝脏和脂肪组织中载脂蛋白2(LCN-2)影响.方法 40只雄性SD大鼠随机分为阴性对照组、高脂模型组、米面组和粗杂粮组,以相应饲料连续喂养8周,测定各组大鼠血清空腹血糖(FBG)和胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);Westernblotting检测各组大鼠肝脏和脂肪组织中LCN-2和过氧化物酶体增殖体激活受体-γ(PPAR-γ)蛋白表达.结果 与阴性对照组比较,高脂模型组和米面组血清FBG和FINS水平明显升高(P<0.05).高脂模型组和米面组HOMA-IR分别为(10.39±1.63)和(10.34±1.36),明显高于阴性对照组(6.85±1.33);与高脂模型组和米面组比较,粗杂粮组HOMA-IR(6.81±1.37)明显下降,粗杂粮组LCN-2在肝脏和脂肪组织中表达明显低于高脂模型组和米面组,PPAR-γ则相反.结论 全谷豆复配式粗杂粮可以激活胰岛素抵抗大鼠PPAR-γ蛋白,进而降低脂肪因子LCN-2表达,改善胰岛素敏感性.     

Fish oil alters T-lymphocyte proliferation and macrophage responses in Walker 256 tumor-bearing rats

OBJECTIVE: We investigated the effect of the dietary ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) from postweaning until adulthood on T-lymphocyte proliferation, T-lymphocyte subpopulations (helper and cytotoxic), and production of cytotoxic mediators by macrophages in tumor-bearing rodents. METHODS: Weanling male Wistar rats received a normal low-fat (40 g/kg of diet) chow diet or a high-fat (300 g /kg) diet that included fish or sunflower oil or blends of fish and sunflower oils to yield omega-6:omega-3 PUFA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, 50% of rats in each group were inoculated with 1 mL of 2 x 10(7) Walker 256 cells. Fourteen days after tumor inoculation, animals were killed and lymphocytes and macrophages were obtained for study. RESULTS: The diets richest in omega-6 PUFA resulted in higher proliferation of thymus, spleen, and gut-associated lymphocytes compared with the chow diet irrespective of tumor burden. In contrast, the fish oil diet resulted in lower proliferation of thymus and spleen lymphocytes compared with the chow diet. Diets rich in omega-6 PUFA decreased the proportion of CD8+ lymphocytes. In non-tumor-bearing and tumor-bearing rats, hydrogen peroxide production by macrophages was highest in rats that consumed diets high in omega-3 PUFAs. Superoxide and nitric oxide production were little affected by the dietary ratio of omega-6 to omega-3 PUFAs. CONCLUSION: Dietary omega-6 and omega-3 PUFA contents alter immune function in non-tumor-bearing and tumor-bearing rats. The omega-3 PUFAs decreased T-cell proliferation but increased hydrogen peroxide production compared with omega-6 PUFAs. Decreased tumor growth and cachexia and increased survival previously reported for fish oil in Walker 256 tumor-bearing rats may be related to improved macrophage function rather than to improved T-cell function.     

Impact of low-level exposure to organophosphates on human reproduction and survival

Despite their widespread and longstanding use for the public good, organophosphate (OP) pesticides have led to many adverse effects on human health. Environmental exposure to OPs and adverse reproductive outcomes in men and women working on or living near farms are increasingly reported worldwide. The aim of the current review is to determine whether exposure to OPs, at levels lower than that which results in clinical manifestations of acute OP poisoning, leads to an adverse impact on fertility, growth and development, and to highlight possible effects for further investigation. There is evidence of impaired fertility due to a reduction in semen quality and possibly lower testosterone levels in exposed males. There is also evidence of impairment of fetal growth and development brought about by prenatal exposure to OPs. Paraoxonase gene (PON1) activity in the fetus and during early childhood makes the fetus and child more vulnerable to OP poisoning, suggesting that OP exposure has a greater impact on fetal and infant growth and development than on adults when exposed to the same concentrations of pesticides. This review raises concerns that exposure to OP pesticides at levels currently regarded as safe adversely affect human reproductive function and survival.     

Increased insulin sensitivity in iron-deficient rats

Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.     

Changes in food intake and stomach contents of tumor-bearing rats after treatment with dopamine antagonists

The appetite-stimulating (orexigenic) potential of the peripheral dopamine (DA) receptor antagonist domperidone was compared with that of the central DA antagonist pimozide in anorexic, tumor-bearing rats. DA antagonists were administered via the intraperitoneal route on Days 7-15 after the subcutaneous implantation of the Walker 256 carcinosarcoma. The doses of domperidone injected were 0.05 and 0.1 mg/kg once daily and 0.1 mg/kg twice daily. The dose of pimozide given was 0.1 mg/kg daily. While all doses of DA antagonists caused an initial drop in body weight and food intake, the body weight of pimozide-injected animals was not reduced significantly (in the early stages of drug treatment) as it was with the various doses of domperidone. There was significantly more food in the stomachs of domperidone- and pimozide-treated animals compared with those of the vehicle-treated, tumor-bearing animals at the time of sacrifice. These results indicate that short- and long-term satiety factors, in addition to gastric motility, should be considered when assessing the orexigenic potential of various drugs.