Streptozotocin-induced type 1 diabetes mellitus alters the morphology,secretory function and acyl lipid contents in the isolated rat parotid salivary gland

Diabetes mellitus (DM) is associated with numerous conditions including hypo-secretion of digestive enzymes. This study investigated the morphology, secretory function (-amylase release) and acyl lipid contents in the isolated parotid gland of STZ-induced diabetic and age-matched control rats in order to provide insights into diabetes-induced salivary insufficiency. The techniques employed included light microscopy, colourimetric and gas chromatography (GC) analysis, respectively. Diabetes mellitus was induced in adult male Wistar rats by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg per kg body weight). Control animals were injected with a similar volume of citrate buffer. The animals were tested for DM 4 days after STZ injection and 2 months later when they were humanely killed for the experiment. The morphological results showed diabetic parotid glands to be extensively infiltrated with lipid droplets of various magnitudes, whereas glands from control animals display normal structure with the absence of lipid droplets. The analysis of parotid secretory function revealed a significant (p < 0.05) dose-dependent decrease in -amylase release in response to noradrenaline (NA) in STZ-treated glands when compared to age-match control parotid glands. Furthermore, the levels of acyl lipids (16:0, 16:1, 18:0 and 18:1) in diabetic parotid glands was significantly (p < 0.01) reduced compared to control glands, along with a reduced ratio of 16:1/16:0. The results indicate DM can elicit changes in the morphology, secretory function and acyl fatty acid quantity in the isolated rat parotid gland. (Mol Cell Biochem 261: 175–181, 2004)     

Effects of ageing on morphology,amylase release,cytosolic Ca2+ signals and acyl lipids in isolated rat parotid gland tissue

Xerostomia (oral dryness sensation) is due to dryness of the oral cavity and it is more prevalent in the elderly. This study investigated the effect of ageing on parotid gland structure and function of control (2-6 months) and aged (12, 16-18 and 22-24 months) rats employing light microscopic, colorimetric, gas chromatographic and microspectrofluorimetric methods to investigate the morphological changes of the parotid glands, amylase release, endogenous lipid distribution and cytosolic free calcium levels, respectively. When compared to controls, age-related changes were apparent in glands obtained from rats aged 16-18 and 22-24 months, which included reduced acinar cell distribution, enlarged parotid ducts with fatty and connective tissue and mast cell infiltrations. Parotid acini from 12, 16-18 and 22-24-month-old glands showed significant (p < 0.05) age-related decreases in amylase release, compared to controls when challenged with acetylcholine (ACh). No change in basal calcium signals was observed in parotid acini from 2-6 to 16-18-month-old-animals. However, stimulation of 16-18-month-old parotid acini with 10(-5)M ACh resulted in a significant (p < 0.001) decrease in both peak and plateau phases of the cytosolic Ca2+ signal when compared to control. Gas chromatography of de novo and essential acyl lipids revealed no changes in the amount of either acyl lipid group in glands obtained from 2-6 to 22-24-month-old animals. Lipid analysis of phospholipid associated acyl chains showed a higher relative proportion of linoleic acid in older glands. The results reveal that ageing is associated with marked and distinct morphological changes including infiltrations of lipids and mast cells of the parotid gland and decreases in amylase release and cytosolic Ca2+ signals.     

The binding of VIP36 and alpha-amylase in the secretory vesicles via high-mannose type glycans

Vesicular integral protein of 36 kDa (VIP36) is an intracellular lectin recognizing high-mannose type glycans and is highly expressed in salivary glands, especially the parotid gland, which secretes alpha-amylase in large quantities. Here immunoelectron microscopy demonstrated that VIP36 was primarily localized to secretory vesicles in the glandula parotis of the rat, where alpha-amylase also resided. A secretory vesicle fraction, prepared by Percoll density gradient centrifugation, contained both VIP36 and alpha-amylase. Moreover, alpha-amylase that was localized to these secretory vesicles contained high-mannose type glycans. In addition, VIP36 coprecipitated with alpha-amylase in an endo H treatment-sensitive manner. These results suggest that VIP36 is involved in the secretion of alpha-amylase in the rat parotid gland.     

Influence of streptozotocin-induced diabetes on hexokinase activity of rat salivary glands

The influence of diabetes on the enzyme hexokinase (HK) was examined in the salivary glands of rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (60 mg/Kg body weight) in overnight fasted rats (180-200 g). The animals were killed 48 hours and 30 days after the induction of diabetes and the submandibular and parotid salivary glands extracted for use. Hyperglycemia was evaluated by determining the blood sugar. The area occupied by each intralobular component, acini, ducts, total parenchyma and stroma was measured, and no differences were observed compared with control. In the soluble fraction of the submandibular gland, no difference in the specific activity of HK was observed, between the diabetic and control animals, however, the activity per gland and per g of tissue showed lower values than control. The specific activity of the bound form was reduced in the diabetic gland. The results obtained for the parotid gland were different from the submandibular. The specific activity of both the soluble and bound forms were increased in the diabetic animals. The DEAE-cellulose column chromatography of the soluble and bound forms of the enzyme from both glands showed a first peak appearing during the washing of the column and two other peaks were eluted by the gradient. Thus, three isoenzymes in the submandibular and parotid salivary glands for the control and diabetic rats have been found.     

Effects of melatonin on the ultrastructure of the golden hamster parathyroid gland.

Ultrastructural changes of the parathyroid glands of melatonin-treated golden hamsters were studied. Many chief cells in the parathyroid glands after 1 hour of administration of melatonin contained poorly-developed Golgi complexes associated with a few prosecretory granules and numerous lipid droplets as compared with those of the control animals. The morphology of the parathyroid glands after 5 hours of administration resembled that of the control animals. Many chief cells in the parathyroid glands after 24 hours of administration had well-developed Golgi complexes and cisternae of the granular endoplasmic reticulum, numerous prosecretory granules, a few lipid droplets and many secretory granules in the peripheral cytoplasm as compared with those of the control animals. The ultrastructure of the parathyroid glands after 48 hours of administration was almost similar to that of the control animals. It is considered that melatonin affects the secretory activity of the parathyroid gland.     

Effects of isoproterenol on the fine structure of the hamster parathyroid gland

Ultrastructural changes of the parathyroid glands of isoproterenol-treated golden hamsters were investigated. Many chief cells in the parathyroid glands after 5 and 10 minutes of administration of isoproterenol contain well-developed Golgi complexes and granular endoplasmic reticulum, numerous prosecretory granules, and many secretory granules in the peripheral cytoplasm as compared with the control animals. Many chief cells in the parathyroid glands after 1, 3, 6 and 12 hours of administration have poorly-developed Golgi complexes, granular endoplasmic reticulum, many secretory granules and numerous lipid droplets as compared with the control animals. The morphology of the parathyroid gland after 30 minutes and 24 hours of administration resembles that of the control animals. It is considered that isoproterenol affects the secretory activity of the parathyroid gland.     

Cellular compartmentation of lysozyme and alpha-amylase in the mouse salivary glands. Immunogold approaches at light and electron microscopy level

The research was planned to study the subcellular distribution of enzymatic secretory products within the secretory structures of the mouse major salivary glands at light and electron microscopy level by immunogold silver stain (IGSS) technique and double-sided post-embedding immunogold binding and silver amplification in order to speculate about their compartmentation. In particular, we experimented the above immunogold labeling approaches to localize the lysozyme and to verify its distribution patterns in relation to another secretion enzyme, alpha-amylase. Co-presence of lysozyme and alpha-amylase was observed in the convoluted granular tubule cells of the submandibular gland and in the demilunar cells of the sublingual gland as well as in the electron-dense regions of the mottled secretory granules in the parotid gland. Exclusive binding patterns of lysozyme were observed in the acinar cells of the submandibular and sublingual glands where alpha-amylase did not occur.     

Low‐power laser irradiation decreases lipid droplet accumulation in the parotid glands of diabetic rats

Lipid droplet accumulation has been related to salivary gland hypofunction in diabetes. In this study, the effect of laser irradiation on the parotid glands (PGs) of diabetic rats was analyzed with regard to its effect on lipid droplet accumulation, intracellular calcium concentration and calmodulin expression. The animals were distributed into 6 groups: D0, D5, D20 and C0, C5, C20, for diabetic (D) and control animals (C), respectively. Twenty‐nine days following diabetes induction, PGs of groups D5 and C5; D20 and C20 were irradiated with 5 and 20 J/cm² of a red diode laser at 100 mW, respectively. After 24 hours, PGs were removed for histological, biochemical, and western blotting analysis. The diabetic animals showed lipid droplet accumulation, which was decreased after irradiation. Ultrastructurally, the droplets were nonmembrane bound and appeared irregularly located in the cytoplasm. Moreover, diabetic animals showed an increased intracellular calcium concentration. In contrast, after laser irradiation a progressive decrease in the concentration of this ion was observed, which would be in agreement with the results found in the increased expression of calmodulin in D20. These data are promising for using laser to decrease lipid droplet accumulation in PGs, however, more studies are necessary to better understand its mechanisms. Micrographs showing decreased lipid accumulation after laser irradiation in light micrographs (LM), and morphology of lipid droplet in transmission electron microscopic (TEM). LM: (A) PGs from nondiabetic rats that did not receive Laser irradiation (LI), (B) PGs from nondiabetic rats that received a dose of 20 J/cm², (C) lipid accumulation (arrows) in the secretory cells from diabetic rats that did not receive irradiation, (D) reduction of lipid accumulation in the secretory cells from diabetic rats that received a dose of 20 J/cm² and TEM: (E) scale bar = 5 μm, (F) scale bar = 1 μm, and (G) scale bar = 0.5 μm.      

糖尿病大鼠性腺及外周血中性激素的改变

目的:研究糖尿病大鼠性腺及外周血中性激素的变化。方法:用放射免疫法检测糖尿病(DM)大鼠,正常(NDM)大鼠和STZ大鼠血清性激素含量,同时称取性腺重量,镜检睾丸、前列腺及附睾的组织形态学改变。结果:DM组睾酮水平显著低于NDM组、STZ组(P<0.01);NDM组与STZ组之间,睾酮水平无显著性差异;DM组促黄体生成素(LH)水平显著高于NDM组、STZ组(P<0.01);NDM组与STZ组之间。LH水平无显著性差异;促卵泡刺激素(FSH)水平在各组之间无显著性差异;HE结果显示,DM组性腺显微结构较NDM组及STZ组明显改变。结论:提示DM严重影响大鼠性腺功能及睾酮的合成分泌,并显著降低大鼠血清睾酮含量。     

Sphingolipids metabolism in the salivary glands of rats with obesity and streptozotocin induced diabetes

Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non‐existent. This is odd given the well‐established link between the both in other tissues (e.g., skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin). Wistar rats were allocated into three groups: control, HFD‐, or STZ‐diabetes. The content of major sphingolipid classes in the parotid (PSG) and submandibular (SMSG) glands was assessed via chromatography. Additionally, Western blot analyses were employed for the evaluation of key sphingolipid signaling pathway enzyme levels. No changes in ceramide content in the PSG were found, whereas an increase in ceramide concentration for SMSG of the STZ group was observed. This was accompanied by an elevation in SPT1 level. Probably also sphingomyelin hydrolysis was increased in the SMSG of the STZ‐diabetic rats, since we observed a significant drop in the amount of SM. PSG and SMSG respond differently to (pre)diabetes, with clearer pattern presented by the later gland. An activation of sphingomyelin signaling pathway was observed in the course of STZ‐diabetes, that is, metabolic condition with rapid onset/progression. Whereas, chronic HFD lead to an inhibition of sphingomyelin signaling pathway in the salivary glands (manifested in an inhibition of ceramide de novo synthesis and accumulation of S1P).     

Effects of hypergravity environment of the ultrastructure of the golden hamster parathyroid gland

The fine structure of the parathyroid glands of golden hamsters exposed to 2, 5 or 10 g environment for 5 h was studied. In the centrifuged hamsters, many secretory granules are located in a peripheral position just beneath the plasma membrane of chief cells, and the Golgi complexes and cisternae of the granular endoplasmic reticulum are significantly increased compared with those of control animals. There are no significant differences between the control and centrifuged animals with regard to secretory granules, large secretory granules, lysosomes, vacuolar bodies and lipid droplets. These findings suggest that the secretory activity of the parathyroid gland may be stimulated in response to hypergravity environment.     

Hydrophobic surface properties of myosin in solution as studied by partition in aqueous two-phase systems: effects of ionic strength,pH and temperature

Summary The effect of gonadectomy (at the 10th day of life) and treatment with sexual steroids (during the first month) upon development of alpha-amylase activity in rat parotid gland has been studied.Alpha-amylase specific activity of parotid glands from 20-day-old orchidectomized rats and from 25-day-old ovariectomized animals was significantly higher than that of intact male and female rats of the same age respectively. Spayed males treated with testosterone (10 g/day on the 13th, 15th, and 17th day) and ovariectomized rats treated with oestradiol (2.5 g/day from the 16th to the 22nd day) showed values of enzymic activity similar to those of normal animals.Results indicate that oestradiol and testosterone have an inhibitory effect upon the increase of alpha-amylase activity in parotid gland during a very defined period of development.Career investigators of Consejo Nacional de Investigaciones Cientificas y Técnicas.     

Alteration of Ca2+‐ATPase activity in the homogenate,plasma membrane and microsomes of the salivary glands of streptozotocin‐induced diabetic rats

Diabetes has been implicated in the dryness of the mouth, loss of taste sensation, sialosis, and other disorders of the oral cavity, by impairment of the salivary glands. The aim of the present study was to examine the plasma membrane, microsomal, and homogenate Ca²⁺‐ATPase activity in the rat submandibular and parotid salivary glands of streptozotocin‐induced diabetes. We have also examined the influence of the acidosis state on this parameter. Diabetes was induced by an intraperitoneal injection of streptozotocin and acidosis was induced by daily injection of NH₄Cl. At 15 and 30 days after diabetes induction, the animals were euthanized and the submandibular and parotid salivary glands were removed and analyzed. Ca²⁺‐ATPase (total, independent, and dependent) was determined in the homogenate, microsomal, and plasma membranes of the salivary glands of diabetic and control rats. Calcium concentration was also determined in the glands and showed to be higher in the diabetic animals. Ca²⁺‐ATPase activity was found to be reduced in all cell fractions studied in the diabetic animals compared with control. Similar results were obtained for the submandibular salivary glands of acidotic animals; however in the parotid salivary glands it was found an increase in the enzyme activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Myocardial and metabolic dysfunction in type 2 diabetic rats: impact of ghrelin

Diabetes mellitus (DM) is commonly associated with metabolic and cardiac dysfunctions. The aim of this study was to examine the effect of ghrelin on metabolic and cardiac dysfunctions in a type-2 diabetes mellitus (T2DM) rat model. For this, 48 male adult Sprague-Dawley rats were divided equally into 4 groups: Group I, fed normal chow, served as normal control group; Groups II-IV, were fed a high-fat diet for 2?weeks followed by injection of streptozotocin (STZ) (35?mg/kg body mass) to create a model of T2DM; Group II, were not treated; Group III, were treated with the vehicle (saline); Group IV, were treated with ghrelin (40?μg/kg body mass) twice daily for 10 days. The untreated diabetic rats showed a significant increase in serum fasting blood glucose, insulin homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), total serum cholesterol (TC), and body mass, with a decrease in high-density lipoprotein cholesterol (HDL-C) (p?< 0.05). Hearts isolated from diabetic rats showed a significant increase in myocardial fat content, a significant decrease in GLUT4, and an increase in acyl-CoA oxidase enzyme mRNA (p?< 0.05). Ghrelin administration for 10?days caused a significant improvement in lipid profile, HOMA index, and body mass, and significantly corrected the myocardial mass, significantly reduced the fat content of the myocardium, significantly increased GLUT4, and decreased acyl CoA oxidase mRNA (p?< 0.05). Thus, ghrelin improves both the metabolic functions and the disturbed energy metabolism in the cardiac muscle of obese diabetic rats.     

Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats

Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (¹H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabetic conditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ (55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM types compared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathways were the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase in the plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesterol and low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DM period. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and can generate ideas for finding targeted drugs.     

苯那普利对糖尿病大鼠肾小球MMP-9影响的实验研究

目的探讨苯那普利对糖尿病大鼠肾小球基质金属蛋白酶-9（MMP-9）表达的影响。方法将雄性SD大鼠30只,随机抽出10只动物作为正常对照组（C组）,其余20只采用腹腔注射STZ制备糖尿病大鼠模型。将这20只造模成功的糖尿病大鼠模型随机分为2组：糖尿病组（DM组）和药物处理组（DB组）。其中药物处理组即DB组大鼠每天应用苯那普利进行治疗性灌胃,C组和DM组用等量自来水灌胃。分别于治疗4、8周后,测定皿糖和内生肌苷清除率,用代谢笼收集24h尿量。利用免疫组织化学染色及图像分析方法,对MMP-9在肾组织不同时间点的含量变化进行定性分析。结果苯那普利治疗组血糖水平和内生肌苷清除率明显降低,与糖尿病模型组相比有显著性差异。免疫组织化学染色显示：MMP-9在正常肾小球有阳性表达;DM组大鼠病程第8周时,MMP-9在肾小球表达明显减弱;DB组大鼠病程第8周时,经苯那普利治疗后,与同期糖尿病组比较表达明显上调。图像分析方法定量分析免疫组织化学染色阳性面积百分比,苯那普利治疗后第4周和第8周糖尿病肾病的大鼠肾小球MMP-9的阳性面积百分比分别为25．55％±3．44％和20．10％±2．11％,与糖尿病组对比有明显的提高（P〈0．01）。结论MMP-9在糖尿病肾小球中的表达随病程进展逐渐减弱,苯那普利可能部分通过上调MMP-9在肾小球中的表达起到保护肾脏的作用。     

Chemical characterization of cytoplasmic lipid droplets in the pheromone-producing cells of the silkmoth,Bombyx mori

Accumulation of lipid droplets within the cytoplasm is a common feature of the pheromone gland cells of many lepidopteran species. The cytoplasmic lipid droplets in the pheromone-producing cells of the silkmoth, Bombyx mori, were effectively extracted by dipping the trimmed glands in acetone for 10 min. In order to analyze the components originating from the lipid droplets, we separated the acetone extracts prepared before and after adult eclosion using HPLC, and specified the peaks showing a similar pattern of stage-dependence to that in the morphological change of the lipid droplets previously reported by Fónagy et al. (Arthropod Struct. Dev. 30 (2001) 113). Finally, we specified the peaks #1-5 and #1a-4a separated by reversed-phase HPLC as lipid droplet contents. Structure elucidation using FAB-MS and MS-MS analyses confirmed that they were triacylglycerols (TGs), and 12 species of TGs were identified as lipid droplet contents. Fatty acyl groups contained in these TGs were limited to five unsaturated C16 and C18 fatty acyl groups (delta 11-hexadecenoate, delta 10,12-hexadecadienoate, delta 9-octadecenoate, delta 9,12-ocatadecadienoate, and delta 9,12,15-ocatadecatrienoate), including the pheromone precursor delta 10,12-hexadecadienoate as a major component. Digestion with porcine pancreatic lipase confirmed that three major TGs eluted in the peaks #3-5 all contained C18 fatty acyl groups at the sn-2 position, indicating that the pheromone precursor is sequestered preferentially at the sn-1 and/or sn-3 position. Present results combined with the fact that the morphological change of the lipid droplets is under the control of PBAN indicate that the role of the cytoplasmic lipid droplets in the pheromone-producing cells is to store the pheromone precursor in the form of TGs and to provide it for pheromone production in response to the external signal of PBAN.     

Polar lipid derangements in type 2 diabetes mellitus: potential pathological relevance of fatty acyl heterogeneity in sphingolipids

While pathological alterations in plasma neutral lipids with type 2 diabetes mellitus (T2DM) has been relatively well-characterized, only limited information is available on the variations in global polar lipidome (glycerophospholipids and sphingolipids) with the disease. To systematically identify polar lipid aberrations associated with early stage T2DM, we quantitatively profiled and compared changes in more than 300 plasma lipid species from distinct groups of T2DM patients against overtly healthy controls. Sphingolipid classes including ceramides, sphingomyelins, lactosylceramides (LacCer) and ganglioside GM3 (GM3) were significantly elevated in mild T2DM with a concomitant decrease in glucosylceramides (GluCer), suggesting the increased conversion of GluCer to LacCer in mild diabetes. Individual GM3 species were altered in T2DM according to their acyl chain lengths. While long-chain GM3s (fatty acyl carbon ≥18) were significantly increased in T2DM, the opposite was observed for GM3 18:1/16:0. Importantly, long-chain GM3 species were negatively correlated with HOMA2-%β and positively correlated with FBG; and could distinguish between healthy individuals and mildly diabetic patients with similar HOMA2-%β. The current study therefore identifies metabolic alterations in sphingolipid pathways as early events in T2DM pathogenesis, and provides hypothesis-generating new insights relevant for larger scale clinical studies aimed at identification of early molecular markers of T2DM.     

Remodeling of liver phospholipidomic profile in streptozotocin-induced diabetic rats

Lipid homeostasis in liver is known to be altered with diabetes mellitus, ultimately leading to liver damage and related complications. The present work aimed to evaluate changes in the liver phospholipid profile after 4 months of uncontrolled hyperglycemia. Twenty Wistar rats were divided into two groups: control and streptozotocin-treated (T1DM). After 4 months, animals were sacrificed and morphological characterization of liver was performed and related with serum markers of hepatic damage. Lipid extracts were obtained from liver and phospholipid (PL) classes were quantified. Lipid molecular species were determined by LC–MS and LC–MS/MS, and fatty acids by GC–MS. Concomitantly with signs of hepatic damage we found variations in the relative amount of phospholipid classes in T1DM, characterized by a decrease in PLs with choline head group, and by an increase in the relative content of other PL classes. A remodeling in PL fatty acyl chains was observed in T1DM liver, with a similar pattern to all the PL classes, and consisting in the reduction of 16:0 and an increase of 18:0 and 18:2 acyl chains. The observed changes in T1DM lipid profile may contribute to the altered membrane properties underlying hepatic damage, worsening the metabolic alterations that characterize T1DM.     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.