不同种类游离脂肪酸对大鼠胰岛素抵抗的影响

目的研究短期血浆游离脂肪酸(FFA)升高对大鼠肝脏和外周胰岛索作用的影响,比较不同饱和程度脂肪酸对大鼠肝脏和外周胰岛素抵抗的作用。方法分别给大鼠静脉输注脂肪乳(多不饱和脂肪酸) 肝素,油酸(OLE,单不饱和脂肪酸),猪油(LO,饱和脂肪酸) 肝素(LOH组)和生理盐水7 h,并在输注的最后2 h,行清醒状态高胰岛素-正血糖钳夹试验,测定血浆葡萄糖、FFA、胰岛素和C肽水平,观察不同脂肪酸对胰岛素介导的葡萄糖利用(GU)和肝葡萄糖生成(HGP)能力的影响。结果与生理盐水组比较,脂肪乳、OLE和．LOH组血浆FFA水平升高(均P＜0．01)。在钳夹状态下,所有脂肪组的HGP高于生理盐水组(均P＜0．01),而OLE组和LOH组的HGP明显高于脂肪乳组(均P＜0．01),所有脂肪组GU下降(均P＜0．01),但是不同脂肪组间GU差异无统计学意义。结论血浆脂肪酸短期升高能引起大鼠肝脏和外周胰岛素抵抗,多不饱和脂肪酸引起的肝胰岛素抵抗小于单不饱和脂肪酸或饱和脂肪酸,不同饱和程度脂肪酸诱导的周围胰岛素抵抗程度相似。     

虎杖苷对非酒精性脂肪性肝病胰岛素抵抗及氧化应激影响的实验研究

[目的]研究虎杖苷治疗对非酒精性脂肪性肝病（NAFLD）胰岛素抵抗（IR）及氧化应激的影响。[方法]健康雄性SD大鼠47只,随机分为5组：正常组（10只）、模型组（10只）、虎杖苷大剂量组（9只）、虎杖苷小剂量组（9只）和双环醇组（9只）。正常组予标准饲料,其他4组给予高脂饲料造模;5组共喂养10周后,从正常组与模型组中各随机挑选1只大鼠,取肝脏做病理切片,证实大鼠NAFLD模型的形成。正常组与模型组予以0．9％氯化钠灌胃,5ml／次;虎杖苷大、小剂量组分别以200mg／（kg·d）、100mg／（kg·d）的虎杖苷混悬液灌胃;双环醇组以100mg／（kg·d）的双环醇混悬液灌胃。给药4周,期间各组大鼠统一用标准饲料饲养。次日大鼠禁食12h后,腹腔麻醉,抽取腹主动脉血5ml,分离血清,检测大鼠血清中氧化应激因子丙二醛（MDA）、总超氧化物歧化酶（T-SOD）、羟自由基（-OH）、谷胱甘肽一孓转移酶（GST）水平及血清总抗氧化能力（T-AOC）水平;试剂盒检测空腹血糖、胰岛素水平,计算IR指数（IRI）和胰岛素敏感指数;ELISA法检测大鼠血清肿瘤坏死因子-α（TNF-α）水平。[结果]高脂饮食饲养10周后,模型组大鼠血清-OH、MDA、TNF-α较正常组均显著增高（P〈0．05～〈0．01）,GST、T-SOD、T-AOC活性降低（P〈0．01）,与模型组相比,虎杖苷治疗后,-OH、MDA、TNF-α浓度降低（P〈0．05〈0．01）,而T-SOD及T-AOC的活性恢复（P〈0．05～〈0．01）,IR明显改善（P〈0．05～〈0．01）。[结论]IR和氧化应激关系密切,氧化应激是发生IR的重要原因之一,虎杖苷的抗氧化应激效应是改善IR的部分机制。     

高游离脂肪酸血症所致胰岛素抵抗与氧化应激的关系

研究高游离脂肪酸(FFA)血症所致大鼠机体氧化应激及胰岛素抵抗之间的相互关系,以及其对机体抗氧化能力的影响,探讨胰岛素抵抗的病理生理机制.经研究证实大鼠高FFA血症不仅使组织活性氧簇生成增加[(886±105 vs 427±42)mmol/L,P<0.05],同时损伤机体抗氧化能力,细胞内还原捌谷胱甘肽生成减少[(272±47 vs 561±36)μmol/L,P<0.05],导致氧化应激,从而促进胰岛素抵抗的形成.     

多不饱和脂肪酸对大鼠肝脏甘油三酯蓄积和胰岛素抵抗的影响

目的研究短期多不饱和脂肪酸增高对大鼠肝脏TG含量和胰岛素抵抗的影响。方法给大鼠输注脂肪乳,行清醒高胰岛素-正血糖钳夹试验,观察脂肪乳对葡萄糖利用和肝葡萄糖产生的影响。结果脂肪乳使血浆FFA和TG升高,使肝脏TG和肝葡萄糖产生亦明显升高,钳夹状态葡萄糖利用显著降低。结论短期多不饱和脂肪酸增高可引起肝脏TG蓄积和胰岛素抵抗。     

Effect of free fatty acids and amino acids on glucagon and insulin secretions in normal and diabetic ducks

Summary The relationship between two metabolites, free fatty acids (FFA) and amino acids (AA), and the two main pancreatic hormones, insulin and glucagon, was studied by infusing small amounts of these metabolites into normal and diabetic Peking ducks, i. e. two days after subtotal pancreatectomy. Infusion of oleic acid (0.365 g/kg/30 min as an emulsion in plasma) indicated a suppressive effect of free fatty acids on glucagon secretion, but was without effect on insulin secretion, in normal as well as in diabetic ducks, indicating that insulin might not be directly involved in the FFA-glucagon feedback in the duck. Infusions of arginine for one hour (1 g/kg/h) into normal ducks, hyperglycaemic normal birds (as a result of glucose infusion: 1 g/kg/h) and diabetic ducks, suggested the persistence of an amino acid effect on glucagon secretion, and a slight reduction of the effect on insulin secretion in diabetes. This suggests that insulin may not be involved in amino acidinduced glucagon secretion in the duck.     

Distinguishing nonalcoholic steatohepatitis from fatty liver: serum-free fatty acids, insulin resistance, and serum lipoproteins.

OBJECTIVES: The prognosis of nonalcoholic fatty liver disease is determined by liver biopsy; steatohepatitis can be progressive whereas fatty liver is benign. Insulin resistance and increased hepatic-free fatty acids are central to the pathophysiology of this disorder. Our objective was to assess whether serum-free fatty acids, lipoproteins, and insulin resistance are increased in steatohepatitis compared with fatty liver and healthy controls, and thus may be potential noninvasive markers for liver disease severity. METHODS: Fifteen subjects with biopsy proven nonalcoholic steatohepatitis, 15 with histological fatty liver, and 15 healthy controls were enrolled. Fasting serum glucose and insulin levels, serum-free fatty acids, HDL, LDL, and cholesterol were collected from each subject. Insulin resistance was calculated using the homeostasis assessment model. RESULTS: Insulin resistance, LDL, and cholesterol-to-HDL ratio values were significantly higher in steatohepatitis, whereas HDL was significantly lower compared with both fatty liver and controls. Free fatty acids were similar in all groups. CONCLUSIONS: Along with insulin resistance, serum LDL, and cholesterol-to-HDL ratio values increase with worsening severity of liver histology, and serum HDL values decline. Free fatty acids, however, do not vary between groups.     

Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated rats

BACKGROUND: Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction. METHODS: For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX. RESULTS: Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding. CONCLUSIONS: Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of 'nutrient abundance' capable of restraining food intake.     

Effects of free fatty acids on insulin secretion in obesity

The prevalence of obesity in Western society has reached epidemic proportions and its aetiological role in the development of type 2 diabetes has made finding an effective treatment for the condition of crucial importance. Of the many consequences of obesity, derangements in glucose metabolism present one of the greatest problems to health. While the role of obesity in causing insulin resistance has received much attention, the effect of obesity on β‐cell failure and the consequent development of type 2 diabetes requires re‐emphasis. In this review, the current understanding of the effects of elevated free‐fatty acids on β‐cell function will be examined, including a discussion of potential mechanisms. In particular, dysregulation of biochemical pathways and alterations in key enzymes, proteins and hormones will be considered as grounds for the progression to a diabetic phenotype.     

血游离脂肪酸与不稳定心绞痛病人胰岛素抵抗的关系

目的探讨无糖尿病的不稳定心绞痛患者血浆游离脂肪酸(freefattyacids,FFA)与胰岛素抵抗(insulinresistance,IR)的关系。方法不稳定心绞痛组为经冠状动脉造影确诊不稳定型心绞痛的无糖尿病患者42例,对照组为经冠状动脉造影排除了冠心病患者30例,行75g葡萄糖口服耐量试验,分别测定空腹、餐后30min、120min血糖、胰岛素及FFA水平。结果伴IR患者在不稳定心绞痛组26例(26/42),对照组为12例(12/30),(P=0.066);在不稳定心绞痛组,伴IR患者空腹和餐后120min,FFA分别为(0.63±0.16)mmol/L和(0.16±0.07)mmol/L;高于无IR患者,空腹和餐后120min值为(0.48±0.21)mmol/L和(0.07±0.06)mmol/L(P<0.05);稳态模型评估胰岛素抵抗(homeostasismodelassay-insulinresistanceindex,HOMA-IR)增高(0.50±0.20与0.36±0.22,P<0.05),胰岛素敏感指数(insulinsensitivityindex,HOMA-ISI)降低(-1.96±0.20与-1.71±0.22,P<0.05);不稳定心绞痛组和对照组伴IR患者比较,FFA明显高于对照组,分别为[(0.63±0.16)mmol/L与(0.48±0.22)mmol/L,P<0.05,(0.16±0.07)mmol/L与(0.08±0.03)mmol/L,P<0.01]。相关分析显示HOMA-IR与体重指数呈正相关(r=0.51,P<0.01);餐后30minFFA与HOMA-IR呈正相关(r=0.44,P<0.05);餐后120minFFA分别与空腹胰岛素(r=0.55,P<0.05)、餐后120min血糖呈正相关(r=0.432,P<0.05);游离脂肪酸曲线下面积(FFAAUC)与HOMA-IR(r=0.492,P<0.05)、体重指数(r=0.94,P<0.0001)、腰围(r=0.41,P<0.05)、臀围(r=0.40,P<0.05)和餐后120min胰岛素(r=0.90,P<0.0001)呈正相关。多重逐步回归分析显示,HOMA-IR与体重指数、餐后120minFFA呈正相关。结论FFA与无糖尿病的不稳定心绞痛患者胰岛素抵抗存在密切关系,餐后120minFFA有可能作为评价这类患者胰岛素抵抗的间接辅助诊断指标。     

Modulation of hepatic glucose production by non-esterified fatty acids in Type 2 (non-insulin-dependent) diabetes mellitus

Summary To study the effect of changes in plasma non-esterified fatty acid concentration on suppression of hepatic glucose production by insulin eight Type 2 (non-insulin-dependent) diabetic patients participated in three euglycaemic, hyperinsulinaemic (108pmol · m^2–1 · min^–1) clamp studies combined with indirect calorimetry and infusion of [3-³H]-glucose and [1-¹⁴C]palmitate; (1) a control experiment with infusion of NaCl 154 mmol/l, (2) heparin was infused together with insulin, and (3) an antilipolytic agent, Acipimox, was administered at the beginning of the experiment. Six healthy volunteers participated in the control experiment. Plasma non-esterified fatty acid concentrations during the insulin clamp were in diabetic patients: (1) 151±36 mol/1, (2) 949±178 mol/l, and (3) 65±9 mol/l; in healthy control subjects 93±13 mol/l. Non-esterified fatty acid transport rate, oxidation and non-oxidative metabolism were significantly higher during the heparin than during the Acipimox experiment (p<0.001). Suppression of hepatic glucose production by insulin was impaired in the diabetic compared to control subjects (255±42 vs 51±29 mol/min, p<0.01). Infusion of heparin did not affect the suppression of hepatic glucose production by insulin (231±49 mol/min), whereas Acipimox significantly enhanced the suppression (21±53 mol/min, p<0.001 vs 154 mmol/l NaCl experiment). We conclude that insulin-mediated suppression of hepatic glucose production is not affected by increased non-esterified fatty acid availability. In contrast, decreased non-esterified fatty acid availability enhances the suppression of hepatic glucose production by insulin.     

n-3多不饱和脂肪酸对高脂诱导胰岛素抵抗大鼠肝脏和骨骼肌胰岛素受体及葡萄糖转运蛋白4的作用

目的探讨n-3脂肪酸对饱和脂肪酸诱导的大鼠胰岛素抵抗(IR)肝脏和骨骼肌胰岛素受体(InsR)及葡萄糖转运蛋白4(GluT-4)的作用。方法45只雄性Wistar大鼠分为对照组、高脂组和n-3脂肪酸组。各组饲养11周后测定有关指标。结果(1)与对照组比较，高脂组大鼠体内脂肪相对含量、空腹血糖(FBG)、血清胰岛素(Ins)、甘油三酯(TG)、胆固醇(TC)、胰岛素抵抗指数(IRI)、肝脏TC和TG含量、肌肉中TG含量均显著升高；而肌肉组织中TC含量无显著改变，高脂组肝脏和肌肉InsR含量、肌肉Glut-4蛋白的相对含量均明显下降。(2)n-3脂肪酸组体内脂肪相对含量、FBG、Ins、TG、TC、IRI、肝脏TC和TG含量、肌肉组织中TG含量较高脂组均明显降低，肝脏InsR含量和肌肉GluT-4较高脂组明显升高。结论适量n-3脂肪酸代替饱和脂肪酸的一部分热量后，可增加IR大鼠肝脏InsR含量和肌肉GluT-4蛋白表达。     

Action of insulin and glucose on the re-esterification rate of free fatty acids in isolated human fat cells

Summary In isolated human fat cells of the greater omentum and the mammary gland, the effect of glucose, fructose, and/or insulin was tested on the re-esterification rate of FFA measured by the balance method. It could be shown that in the absence of glucose no re-esterification activity was demonstrable. Glucose alone or fructose alone stimulated the re-esterification of FFA dose-dependently in isolated fat cells of the greater omentum, and to a minor degree in fat cells of the mammary gland. Insulin had no effect on the re-esterification rate of FFA in the presence or absence of glucose or fructose, whereas it significantly stimulated the incorporation of glucose-C into CO₂ and lipids. It is concluded that the re-esterification of FFA in human adipose tissue, at least in vitro, is mainly controlled by glucose without need for insulin.Preliminary results of this investigation were presented at the 6th Annual Meeting of the EASD, Warsaw, 1970.     

Artificial induction of intravascular lipolysis by lipid-heparin infusion leads to insulin resistance in man

Summary Although extensive evidence indicates that free fatty acids can decrease glucose utilization in vitro, it is still controversial how an increase in lipolysis affects glucose metabolism in man. To test the hypothesis that an increase in lipolysis is related to insulin resistance, we examined the effect of lipid-heparin infusion on glucose metabolism in ten normal subjects by the euglycaemic glucose clamp technique and isotopic determination of glucose turnover. In the control euglycaemic clamp studies with insulin infusion at 0.2 and 1.0 mU·kg^–1·min^–1, endogenous glucose production was suppressed from the basal rate of 2.0±0.3 mg· kg^–1min^–1 to 1.1±0.7 mg·kg^–1·min^–1 and -0.4±0.7mg· kg^–1min^–1 respectively. Glucose utilization increased from the basal rate of 2.0±0.3 mg·kg^–1min^–1 to 2.3±0.5mg· kg^–1min^–1 and 5.9±1.8 mg·kg^–1min^–1 respectively. When the euglycaemic clamp studies were coupled with lipid-heparin infusion at comparable low and high rates of insulin infusion, endogenous glucose production increased (1.8± 0.7 mg·kg^–1·min^–1, p<0.001, and 0.3±0.6 mg·kg^–1· min^–1, p<0.05, respectively), and glucose utilization decreased (2.1±0.3 mg·kg^–1·min^–1, not significant, and 3.2±0.7 mg·kg^–1·min^–1, p<0.001 respectively). These data suggest that the artificial induction of intravascular lipolysis by lipid-heparin infusion leads to a state of insulin resistance in man.     

Effect of estrogens on blood sugar,serum insulin and serum free fatty acids,and pancreas cytology in female dogs

Summary We analyzed the changes in blood sugar (BS), serum immunoreactive insulin (IRI), circulating free fatty acids (FFA) and pancreatic cytology caused by estrogenization at low pharmacological dosage in female dogs. Vehicle-injected and untreated controls (anestrus) were studied as well. Neither mean basal BS nor basal serum IRI was modified by the treatments, while the mean basal serum FFA value was raised. Glucose tolerance was not modified by the estrogens while glucosey-mean was significantly raised. Hyperglycemia was higher for a longer time in estrogenized animals compared to both controls, while the profiles of hyperinsulinemia coincided. In the estrogen-treated bitches, the pancreatic B-cells contained scarse brown-stained granules near their vascular pole, as shown by an immunochemical method. In the peripheral part of the pancreas, near the acini, some solitary, poorly β-granulated B-cells were present. During the IVGTT, serum FFA reached lower values for a longer time in the estrogenized bitches as compared to those found in both control groups. Insulin-induced hypoglycemia in the estrogenized animals coincided with the one evoked in the vehicle controls; in the semilog relationship of serum IRI and time,y-mean was lower than that observed in oil-injected controls, and insulin space was larger. The serum FFA levels of the estrogenized bitches, very high in the basal conditions, did not respond to insulin administration, and were above those found in untreated controls and also in vehicle-injected controls just at the beginning of the test. These results are discussed. We came to the conclusion that estrogenization causes some glucose intolerance in bitches while insulin sensitivity remains normal in the IVITT as studied measuring BS. The glucose intolerance is thought to be related to a reduction in glucose space and occurs despite the normality of the serum IRI response. The pancreas must have an intense secretory responsein vivo so as to maintain normal IRI activity despite degranulation of the islets of Langerhans and poor islet hypertrophy and neoformation. The serum FFA changes are thought to contribute towards the tendency to adiposity in these animals. Sponsored by ‘Alberto J. Roemmers Foundation’, by ‘Lucio Cherny Foundation’, The University of Buenos Aires (S.E.C.Y.T., Res. Grant No. 100-301-10-127), and The ‘Consejo Nacional de Investigaciones Cientificas y Técnicas’ (C.O.N.I.C.E.T., Res. Grant No. 2304-h/76), Argentina; this study was partly presented at the 6th Bolivian Congr. of Endocrinology, La Paz, Bolivia. November 1–5, 1977, and at the 13th Scientific Meeting of the Argentine Association of Experimental Pharmacology, Mar del Plata, Argentina, November 9–12, 1981. Established investigator (C.O.N.I.C.E.T.). Postgraduate technician (C.O.N.I.C.E.T.).     

Effect of estrogens on blood sugar,serum insulin and serum free fatty acids,and pancreas cytology in female dogs

Summary We analyzed the changes in blood sugar (BS), serum immunoreactive insulin (IRI), circulating free fatty acids (FFA) and pancreatic cytology caused by estrogenization at low pharmacological dosage in female dogs. Vehicle-injected and untreated controls (anestrus) were studied as well. Neither mean basal BS nor basal serum IRI was modified by the treatments, while the mean basal serum FFA value was raised. Glucose tolerance was not modified by the estrogens while glucosey-mean was significantly raised. Hyperglycemia was higher for a longer time in estrogenized animals compared to both controls, while the profiles of hyperinsulinemia coincided. In the estrogen-treated bitches, the pancreatic B-cells contained scarse brown-stained granules near their vascular pole, as shown by an immunochemical method. In the peripheral part of the pancreas, near the acini, some solitary, poorly β-granulated B-cells were present. During the IVGTT, serum FFA reached lower values for a longer time in the estrogenized bitches as compared to those found in both control groups. Insulin-induced hypoglycemia in the estrogenized animals coincided with the one evoked in the vehicle controls; in the semilog relationship of serum IRI and time,y-mean was lower than that observed in oil-injected controls, and insulin space was larger. The serum FFA levels of the estrogenized bitches, very high in the basal conditions, did not respond to insulin administration, and were above those found in untreated controls and also in vehicle-injected controls just at the beginning of the test. These results are discussed. We came to the conclusion that estrogenization causes some glucose intolerance in bitches while insulin sensitivity remains normal in the IVITT as studied measuring BS. The glucose intolerance is thought to be related to a reduction in glucose space and occurs despite the normality of the serum IRI response. The pancreas must have an intense secretory responsein vivo so as to maintain normal IRI activity despite degranulation of the islets of Langerhans and poor islet hypertrophy and neoformation. The serum FFA changes are thought to contribute towards the tendency to adiposity in these animals. Sponsored by ‘Alberto J. Roemmers Foundation’, by ‘Lucio Cherny Foundation’, The University of Buenos Aires (S.E.C.Y.T., Res. Grant No. 100-301-10-127), and The ‘Consejo Nacional de Investigaciones Cientificas y Técnicas’ (C.O.N.I.C.E.T., Res. Grant No. 2304-h/76), Argentina; this study was partly presented at the 6th Bolivian Congr. of Endocrinology, La Paz, Bolivia, November 1–5, 1977, and at the 13th Scientific Meeting of the Argentine Association of Experimental Pharmacology, Mar del Plata, Argentina, November 9–12, 1981. Established investigator (C.O.N.I.C.E.T.). Postgraduate technician (C.O.N.I.C.E.T.).     

Fatty acids and insulin resistance in muscle and liver

Free fatty acids (FFAs) circulate round the body and represent important nutrients and the key oxidative fuel for the heart and resting skeletal muscle. In addition, FFAs are thought to be potent signalling molecules. Growing evidence indicates that FFAs may be involved in type 2 diabetes mellitus and obesity by mediating insulin resistance. In 1963, it was postulated that accumulated glucose-6-phosphate as a result of increased FFA oxidation leads to decreased glucose uptake. An alternative hypothesis is that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity, which appears to be a consequence of decreased insulin receptor substrate-1-associated phosphatidyl inositol 3 kinase activity. Moreover, FFAs can arise locally, and increased intramyocellular and hepatocellular lipids have been shown to be associated with insulin resistance. This paper reviews the main aspects of FFA metabolism in the development of insulin resistance in skeletal muscle and liver, as well as the role of ectopic lipid deposits as a local source of FFAs. Finally, the role of thiazolidinediones as modulators of FFA-induced insulin resistance will be discussed.     

单不饱和脂肪酸膳食通过缓解氧化应激改善糖耐量正常人群的胰岛素敏感性

20例健康受试者分别接受单不饱和脂肪酸饮食、多不饱和脂肪酸饮食、饱和脂肪酸饮食3d,单不饱和脂肪酸可以改善机体的氧化应激状态,从而改善胰岛素敏感性.     

Effect of insulin and growth hormone on rat heart and liver oxidative stress in control and caloric restricted animals

In order to know if insulin-like signalling is involved in the control of oxidative stress in mammalian tissues in relation to aging, ad libitum-fed and caloric restricted Wistar rats were treated during 2 weeks with GH and insulin. The most consistent effect of the hormonal treatments was an increase in plasma IGF-1 levels. Caloric restriction during 6 weeks decreased ROS generation and oxidative DNA damage in heart mitochondria and this was reversed by insulin treatment. The decrease in oxidative damage to liver nuclear DNA induced by caloric restriction was also reversed by GH and insulin. In the liver, however, insulin and GH decreased mitochondrial ROS generation while they increased oxidative damage to mitochondrial DNA. GH and insulin decreased three different markers of oxidative modification of liver proteins, while they increased lipoxidation-dependent markers. This last result is related to the increase in phospholipid unsaturation induced in the liver by both hormones. The results suggest that the idea that insulin-like signalling controls oxidative stress in mammals cannot be generalized since both prooxidant and protective effects of GH and insulin are observed depending on the particular parameter and tissue selected.