Ultrastructural alterations in cardiac muscle of diabetic BB Wistar rats

Summary The cardiac muscle of BB Wistar rats suffering from diabetes for 8 and 16 weeks (8-Wk and 16-Wk of DM) were examined by light and electron microscopy. The diabetic rats were kept alive by injections of small doses of insulin and exhibited severe hyperglycaemia, glycosuria and weight loss. The heart/body weight ratio of all diabetic groups was greater than that of age matched controls. Over the experimental period, the left ventricular myocardium of the diabetic BB rats sustained damage that was progressively more serious with the duration of the diabetic state. In BB rats after 8-wk of diabetes the myocardium contained large numbers of lipid droplets and glycogen granules around mitochondria which showed patchy swelling, and slight loss of myofilaments. Disruption of mitochondrial membranes and extensive loss of myofilaments were seen in rats diabetic for 16 wk. In addition, dilatation of the sarcoplasmic reticulum-transverse tubular system, formation of a contraction band and myelin bodies and widening of the intercellular space at the fasciae adherens of the intercalated disc were characteristically observed in BB rats after 16-wk of diabetes. However, there were no evident alterations in the capillaries of any diabetic BB rats. Morphometric analyses showed the volume percentage of myofibrils in diabetic rats to be significantly decreased when compared with controls. The loss of myofibrillar elements may be a primary damage induced by insulin deficiency. The formation of contraction bands suggests Ca²⁺ overload caused by diabetic metabolic disturbances.     

Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.

Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.     

大鼠心肌细胞粘着斑蛋白α-catenin表达的增龄变化

目的　探讨大鼠心肌细胞发育过程中粘着斑蛋白α -catenin的表达分布方式以及增龄变化规律。方法　应用S -P免疫组化方法分别对大鼠的胎儿、新生儿、幼年、青年、中年和老年大鼠的心肌细胞粘着斑蛋白α-catenin的表达进行检测。结果　细胞粘着斑蛋白α -catenin在大鼠的心房、心室、乳头肌、室间隔等处均有表达。胎鼠心肌细胞中粘着斑蛋白α -catenin分散分布于细胞膜和胞浆中 ;新生大鼠心肌细胞的连接处见有α-catenin的免疫标记颗粒 ;幼年时期α -catenin的免疫标记颗粒大部分集中在心肌细胞末端的闰盘处 ;青年、中年和老年大鼠α -catenin的免疫标记典型的分布在心肌细胞末端的闰盘处。结论　在大鼠心肌发育过程中 ,α -catenin的表达分布存在增龄变化 ;粘着斑蛋白α -catenin的分布方式与闰盘的发育是一致的。     

Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression

Streptozotocin-diabetic rats, an animal model for diabetes mellitus, show learning deficits and impaired long-term potentiation in the CA1-field of the hippocampus. The present study aimed to further characterize the effects of streptozotocin-diabetes on N-methyl-D-aspartate receptor-dependent long-term potentiation in the CA1-field, to extend these findings to N-methyl-D-aspartate receptor-dependent and independent long-term potentiation in other regions of the hippocampus and to examine effects on long-term depression. First, the effect of diabetes duration on long-term potentiation in the CA1-field was determined. A progressive deficit was observed after a diabetes duration of six to eight weeks, which reached a maximum after 12 weeks of diabetes and remained stable thereafter. Next, long-term potentiation was examined in the dentate gyrus and in the CA3-field after 12 weeks of diabetes. Both were found to be impaired compared to controls. Finally, long-term depression was examined in the CA1-field of the hippocampus after 12 weeks of diabetes and found to be enhanced in slices from diabetic rats compared to controls. Changes in synaptic plasticity were observed in hippocampal slices from streptozotocin-diabetic rats. Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation was impaired in the CA1-field and dentate gyrus and expression of N-methyl-D-aspartate receptor-independent long-term potentiation was impaired in the CA3-field. In contrast, expression of long-term depression was facilitated in CA1. It is suggested that this combination of changes in plasticity may reflect alterations in intracellular signalling pathways.     

人心肌细胞粘着斑蛋白α-catenin表达的增龄变化

目的　探讨在人心脏发育过程中心肌细胞粘着斑蛋白α catenin表达的增龄变化规律。方法　应用S P免疫组化方法分别对新生儿和成年人的心肌细胞α catenin的表达进行检测。结果　细胞粘着斑蛋白α catenin在心房、心室、乳头肌、室间隔等处的心肌细胞中均有表达。新生儿时期大量的α catenin呈斑块状聚集在心肌的端闰盘处 ,少量分布于心肌细胞的侧面连接处和胞浆中 ;成年人心肌细胞的α catenin典型地分布于细胞末端的闰盘处。结论　在人的心肌发育过程中 ,α catenin的表达分布存在增龄变化 ;α catenin的分布方式与闰盘的发育是一致的     

Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.     

Reversibility of the structural effects of pressure overload hypertrophy of cat right ventricular myocardium

The purpose of the present quantitative structural study was to determine whether the histological alterations seen in pressure overloaded myocardium return to normal, as in vitro contractile function does, upon removal of the pressure overload stimulus. Three experimental groups of four cats each were studied: a group with pulmonary artery banding to create a pressure overload, a group that had been subjected to an equivalent duration of pressure overload and then had that pressure overload removed, and a group of sham-operated controls. Seven to 10 weeks after each operative procedure, the right ventricular pressure was elevated only in the pulmonary artery-banded group. The right ventricle/body weight ratio was significantly increased in the pressure overloaded group only. The body weight at sacrifice, the left ventricle/body weight ratio, and the right ventricular end-diastolic pressure did not differ significantly in the three groups. The striking histological changes in the right ventricular myocardium hypertrophing in response to a pressure overload were the decrease in the volume density of cardiocytes and the increase in connective tissue in papillary muscles. These were reversed when the pressure overload was removed. This study demonstrates that when a pressure overload is removed, myocardial structure returns to normal as the function returns to normal. Given the critical importance of the proportion of cardiocytes and connective tissue components to both systolic and diastolic cardiac function, these data support the hypothesis that the abnormal proportions of these structures provide a potential morphological basis for at least some of the functional abnormalities observed in pressure overload hypertrophy of the cat right ventricle.     

Ultrastructural Changes in Muscular Dystrophy: I. Cardiac Tissue of Piglets Deprived of Vitamin E and Selenium

The ultrastructure of cardiac tissue from neonate, 3-, 6-, 8-, and 12-week-old piglets, born of vitamin E- and selenium-deprived sows was studied. A progression of lesions occurred in nonmuscular components of this tissue; the first lesion appeared in connective tissue elements. Fibroblasts and the extracellular compartment appeared most severely altered in the neonate, and progressive vascular damage was very evident from 3 to 12 weeks of age. Similarly, neuronal elements appear altered at 3 weeks and were almost nonevident in areas showing marked lesions at 8 and 12 weeks. Fairly extensive alterations were evident in all of these elements before any marked changes become evident in the muscle. The relevance of these observations is discussed in relation to the etiology of the disease.     

Studies of the lung in diabetes mellitus

Summary To evaluate the effects of chemically induced diabetes on lung tissue, we examined the ultrastructure of the lung of alloxan-induced diabetic rats. Fifty male Wistar rats were made diabetic by a single intraperitoneal injection of alloxan (200 mg/kg of body weight): they were sacrificed from one to four weeks later. The alloxan-induced diabetes produced significant morphological alterations in the lung. These include marked dilatation of the cisterna of the granular endoplasmic reticulum, dilation of the Golgi saccules and the appearance of glycogen granules as a cluster in the cytoplasm of the granular pneumocytes and the interstitium. These findings were well correlated with the severity of diabetes mellitus. The altered granular pneumocytes were observed in about 50% of animals and in most (87.5%) of the observed pneumocytes 2 weeks and 4 weeks after alloxan treatment respectively. The average number of lamellar inclusion bodies per granular pneumocyte decreased to about half of that of the control in diabetic rats 4 weeks after alloxan treatment, and minimum thickness of the capillary basement membrane was approximately 35% thicker than that of the control (diabetics; 879±189 Å, controls; 649±100 Å).The ultrastructural alterations of the lung in diabetic rats indicate disorders in the pulmonary capillaries and in the metabolism of pulmonary surfactant, which may cause pulmonary dysfunction in diabetic patients.     

Stereological assessment of pancreatic beta-cell mass development in male Zucker Diabetic Fatty (ZDF) rats: correlation with pancreatic beta-cell function

The present study was initiated to improve our understanding of pancreatic beta‐cell dynamics in male Zucker Diabetic Fatty (ZDF) rats and hence provide a framework for future diabetes studies in this animal model. Male ZDF rats from 6, 8, 10, 12, 14, 16, 20 and 26 weeks of age were subjected to an oral glucose tolerance test (OGTT). The animals were then euthanized and pancreases were removed for morphometric analyses of pancreatic beta‐cell mass. As evident by a marked fourfold increase in insulin secretion, insulin resistance developed rapidly from 6 to 8 weeks of age. Simultaneously, the pancreatic beta‐cell mass expanded from 6.17 ± 0.41 mg at 6 weeks of age, reaching a maximum of 16.5 ± 2.5 mg at 16 weeks of age, at which time pancreatic beta‐cell mass gradually declined. The corresponding changes in glucose/insulin homeostasis were analysed using a standard insulin sensitivity index (ISI), an area under the curve (AUC) glucose‐insulin index, or simple semi‐fasted glucose levels. The study demonstrated that male ZDF rats underwent rapid changes in pancreatic beta‐cell mass from the onset of insulin resistance to frank diabetes coupled directly to marked alterations in glucose/insulin homeostasis. The study underscores the need for a critical co‐examination of glucose homeostatic parameters in studies investigating the effects of novel anti‐diabetic compounds on pancreatic beta‐cell mass in the male ZDF rat. A simple assessment of fasting glucose levels coupled with information about age can provide a correct indication of the actual pancreatic beta‐cell mass and the physiological state of the animal.     

Effects of streptozotocin-induced diabetes on leg muscle contractile properties and motor neuron morphology in rats

Skeletal muscle fiber subtypes are differentially sensitive to diabetes-related pathology; For example, fast-twitch muscles exhibit severe decreases in contraction force while slow-twitch muscles demonstrate prolonged half-relaxation time. However, such alterations have only been examined after a relatively short period following diabetes onset, with no information available regarding muscle damage caused by longer disease periods (>20 weeks). This study examined alterations in the contractile properties of the medial gastrocnemius (fast-twitch) and soleus (slow-twitch) muscles, as well as morphological changes in their motor neurons 12 and 22 weeks after diabetes onset. Adult male Wistar rats were divided into diabetic (12- or 22-week post-streptozotocin injection) and age-matched control groups. Electrically evoked maximum twitch and tetanic tension were recorded from leg muscles. Additionally, motor neuron number and cell body size were examined. At 12 weeks after diabetes onset, decreases in twitch force were observed predominantly in medial gastrocnemius muscles, while soleus muscles exhibited prolonged half-relaxation time. However, these differences became ambiguous at 22 weeks, with decreased twitch force and prolonged half-relaxation time observed in both muscles. On the other hand, reduction in soleus motor neurons was observed 12 weeks after diabetes onset, while medial gastrocnemius motor neurons were diminished at 22 weeks. These data indicate that experimental diabetes induces differential damage to medial gastrocnemius and soleus muscles as well as motor neurons. These diabetes-induced differences may partly underlie the differential deficits observed in gastrocnemius and soleus.     

Independent alterations in the central and peripheral somatosensory pathways in rat diabetic neuropathy

Peripheral and central diabetic neuropathies were studied in streptozotocin-diabetic rats, using behavioral, biochemical and electrophysiological techniques. Diabetic rats showed thermal hypoalgesia and decreasing motor nerve conduction velocity at 4 and 8 weeks of diabetes. In addition, amplitude of the evoked potential recorded in primary somatosensory cortex after stimulation of the sciatic nerve was markedly reduced at 8 weeks of diabetes. This decrease was accompanied by decreases in GluR2/3 AMPA receptor subunits. These changes seem to be specific to the somatosensory system and to originate in higher centers since they were not present in the hippocampus and were not observed at the level of gracilis nucleus. Insulin-like growth factor I (IGF-I) treatment reversed the reduced thermal sensitivity and peripheral nerve conduction velocity but did not reverse changes in the CNS, suggesting that once initiated, both anomalies may develop independently in this model of diabetic neuropathy. In conclusion, the results indicate that diabetes induces a wide spectrum of alterations in the central somatosensory system that are independent of the decreases in peripheral sensory transmission that could be responsible for the disturbances in somatosensory perception observed in diabetes.     

姜黄素类似物L6H4对2型糖尿病大鼠心肌的保护作用

 目的: 探讨姜黄素类似物L6H4对2型糖尿病心肌病大鼠的保护作用及机制。方法: 雄性SD大鼠40只,随机均分为正常对照(NC)组、高脂(HF)组、高脂治疗(FT)组、糖尿病(DM)组和糖尿病治疗(DT)组。采用高脂饮食加链脲佐菌素诱导2型糖尿病模型,用L6H4治疗8周。生化法测血糖及血脂水平,ELISA法测血清脂联素(APN)水平,放射免疫法测大鼠血清胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR),Masson染色和电镜观察心肌形态改变,免疫组化测心肌脂联素受体1 (AdipoR1)及转化生长因子β1(TGF-β1)蛋白的表达。Western blot法检测大鼠心肌内AdipoR1蛋白表达量。结果: HF组及DM组大鼠血糖、血脂、胰岛素、HOMA-IR及TGF-β1蛋白水平较NC组均有升高,L6H4治疗后均下降;HF组及DM组大鼠血清APN水平及心肌AdipoR1较NC组均有下降,L6H4治疗后均升高。DM组和HF组大鼠心肌纤维化,线粒体肿胀,嵴紊乱,部分消失,经L6H4干预后,大鼠心肌的形态学损害明显减轻。结论: L6H4对2型糖尿病大鼠的心肌具有保护作用;血清APN浓度增加,心肌AdipoR1蛋白表达增强,及APN抑制TGF-β1的表达可能参与其中。     

2型糖尿病大鼠早期血清cTnI水平与心功能的变化

目的:研究2型糖尿病大鼠早期血清心肌肌钙蛋白I(cTnI)的水平及心功能变化,探讨早期2型糖尿病大鼠血清cTnI水平与糖尿病心肌损伤发生发展之间的关系,明确cTnI在糖尿病心肌病发生发展中的作用。方法:通过高脂饮食联合链脲佐菌素建立2型糖尿病大鼠模型,实验将大鼠分为正常对照组、糖尿病2周模型组及4周模型组,超声心动图检测心功能相关指标,血清检测空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹胰岛素(FINS)及cTnI水平,HE染色法观察心肌病理结构变化,Western blot法检测心肌cTnI蛋白表达变化,通过上述指标变化分析2型糖尿病大鼠早期血清cTnI与大鼠心功能改变之间的关系。结果:与正常组比较,2型糖尿病大鼠TC、TG、LDL-C水平显著升高,HDL-C水平显著降低;糖尿病大鼠4周模型组与2周模型组相比较,TC、TG、LDL-C水平升高更明显,HDL-C水平降低更显著(P0.01);显微镜下糖尿病组大鼠心肌可见局灶性心肌细胞变性、坏死;糖尿病组大鼠相对于正常对照组血清及心肌cTnI表达显著增加(P0.01),且4周模型组比2周模型组增加更明显。结论:糖尿病大鼠早期即出现cTnI水平升高和心功能改变,有望为糖尿病心肌病的早期诊断和治疗提供理论依据。     

Electrophysiological changes in rat ventricular and atrial myocardium at different stages of experimental diabetes

Action potential configuration in ventricular and atrial myocardium, as well as rate-dependent changes in ventricular action potential duration (APD) were studied and compared in healthy and diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg kg^–1 i.v.). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (2, 6, 10 and 18 weeks after STZ-treatment). Untreated age-matched animals were used as controls. Both depolarization and repolarization were significantly retarded following STZ-treatment. However, the time course of development of diabetic changes in atrial and ventricular myocardium was different. APD was significantly lengthened from week 2 of diabetes in ventricular, but only from week 6 in atrial preparations. In atrial myocardium, lengthening of APD was more pronounced at early rather than late phases of repolarization. The maximum rate of depolarization (V_max) was significantly reduced from the 6th week of diabetes in both preparations. No differences were observed in action potential amplitude (except at week 18) and in the resting membrane potential in diabetic rats. Diabetic ventricular preparations showed a positive APD-frequency relationship at any level of repolarization, in contrast to control muscles, where APD₂₅ and APD₅₀ values lengthened. But APD₇₅ and APD₉₀ values were not changed significantly with increase in the pacing frequency. The results indicate that development of diabetic alterations are not fully identical in atrial and ventricular myocardium of the rat, probably owing to differences in density and kinetics of ionic currents responsible for atrial and ventricular action potentials.     

Insulin Prevents Latent Skin Lesions by Inhibiting the Generation of Advanced Glycation End Products in Streptozotocin-Induced Diabetic Rats

The preventive effect of insulin on latent skin lesions in streptozotocin-induced diabetic rats was investigated. Diabetes was induced in 72 male Sprague–Dawley rats, with 36 rats serving as the control group. Half of the diabetic rats were treated with insulin, and the other half were injected with vehicle. Skin tissues were collected 4, 8, and 12 weeks after the initiation of insulin therapy for measurement of glucose, collagen-related fluorescence and advanced glycation end product (AGE) expression, and histological observation. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibers, and an increase in the infiltration of inflammatory cells, in addition to a significant increase in blood glucose and AGE expression. These effects were greatly ameliorated by insulin therapy. Insulin therapy in early-stage diabetes mellitus prevents potential skin lesions, possibly by inhibiting AGE formation and inflammatory reactions following glycemic control. Xiangfang Chen and Weidong Lin contributed equally to this work.     

Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes

Ultrastructural changes in heart muscle due to chronic diabetes subsequent to a single injection of streptozotocin (65 mg/kg body wt, i.v.) were studied in rats. Presence of diabetes was indicated by hyperglycaemia (plasma glucose, control, 120 +/- 7; diabetic, 448 +/- 21 mg/dl) as well as hypo-insulinaemia (plasma insulin, control, 25.6 +/- 5.2; diabetic, 11.2 +/- 0.5 microU/ml). After 8 weeks of diabetes, the hearts were processed for electron microscopic examination. Cardiac muscle cells in diabetic hearts showed condensation of nuclear chromatin and folding of nuclear membranes. Swelling of mitochondria, clearing of mitochondrial matrix and incorporation of lysosomal membranes into mitochondrial matrix was also noted. A marked increase in both lysosomes and lipid droplets was apparent. Focal areas in diabetic hearts showed contracted sarcomeres, myofibrillar degeneration and separation of the intercalated disc. Atherosclerotic plaque formation as well as structural changes in the smooth muscle or endothelial cells in the small arteries, arterioles or capillaries were not seen to accompany the structural changes in the cardiac muscle cells of the diabetic hearts. This study provides strong evidence for the occurrence of primary myocardial disease in streptozotocin-induced chronic diabetes.     

Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes.

Ultrastructural changes in heart muscle due to chronic diabetes subsequent to a single injection of streptozotocin (65 mg/kg body wt, i.v.) were studied in rats. Presence of diabetes was indicated by hyperglycaemia (plasma glucose, control, 120 +/- 7; diabetic, 448 +/- 21 mg/dl) as well as hypo-insulinaemia (plasma insulin, control, 25.6 +/- 5.2; diabetic, 11.2 +/- 0.5 microU/ml). After 8 weeks of diabetes, the hearts were processed for electron microscopic examination. Cardiac muscle cells in diabetic hearts showed condensation of nuclear chromatin and folding of nuclear membranes. Swelling of mitochondria, clearing of mitochondrial matrix and incorporation of lysosomal membranes into mitochondrial matrix was also noted. A marked increase in both lysosomes and lipid droplets was apparent. Focal areas in diabetic hearts showed contracted sarcomeres, myofibrillar degeneration and separation of the intercalated disc. Atherosclerotic plaque formation as well as structural changes in the smooth muscle or endothelial cells in the small arteries, arterioles or capillaries were not seen to accompany the structural changes in the cardiac muscle cells of the diabetic hearts. This study provides strong evidence for the occurrence of primary myocardial disease in streptozotocin-induced chronic diabetes.     

Efficacy of zinc oxide nanoparticles in attenuating pancreatic damage in a rat model of streptozotocin-induced diabetes

Zinc oxide nanoparticles (ZnO NPs) therapy is a promising strategy for treatment of several diseases. We aimed to investigate the therapeutic potential of ZnO NPs in ameliorating the histopathological and functional alterations in the pancreas of a rat model of streptozotocin-induced diabetes. Rats were randomized into control, diabetic and ZnO NPs-treated diabetic groups. Biochemical assays of blood glucose and serum insulin were performed. Pancreas specimens were processed for light and electron microscope examinations. ZnO NPs effectively reversed diabetes-induced pancreatic injury, as evidenced by the structural and ultrastructural improvement and confirmed by biochemical normalization of blood glucose and serum insulin.     

Tungstate administration improves the sexual and reproductive function in female rats with streptozotocin-induced diabetes

BACKGROUND: Diabetes induces great alterations in female reproductive function. We analyzed the effects of tungstate, an anti-diabetic agent, on the reproductive function of healthy and diabetic female rats. METHODS: Healthy and streptozotocin-induced diabetic rats were treated with sodium tungstate (2 mg/ml in their drinking water) for 12 weeks. Markers of reproductive function and diabetes were measured in serum, and in uterus and ovaries by Western blot or RT-PCR. Reproductive function was also assessed by mating. RESULTS: Diabetic rats showed great impairment of libido, which was accompanied by a total loss of fertility (P < 0.05) and a decrease in the serum levels of FSH (P < 0.05) and LH (P < 0.05) compared with healthy rats. Tungstate treatment of diabetic rats partially recovered libido while fertility rate increased to 66.6%. This improvement was accompanied by a recovery of serum FSH (to a level higher than healthy rats) and LH. Moreover, tungstate treatment normalized ovarian expression of GLUT 3 hexose transporter, and estrogen, progesterone and FSH receptors, whereas only GLUT 3 and FSH receptors were normalized in the uterus. CONCLUSIONS: Our results indicate that the alterations in female reproduction in diabetes were partially reversed after tungstate treatment by a mechanism(s) involving the normalization of serum FSH and LH levels, and ovarian and uterine expression of FSH receptors and GLUT3.