Experimental Models Of Diabetes Research Articles

Protective Effect of Pelargonium graveolens Essential Oil Against Alloxan-Induced Diabetes and Oxidative Stress in Rats

Oxidative stress occurs in diabetic patients and experimental models of diabetes. The antioxidant property of Pelargonium graveolens essential oil (PGEO) might have a beneficial effect in ameliorating the disease. In this context, the aim of the present study was to investigate the effects of PGEO on oxidative stress in alloxan-induced diabetes in rats. The antidiabetic and antioxidant activities were evaluated after sub-acute intraperitoneal injection of male rats to 42.5 mg/kg b.w. essential oil for 21 days. In results, we found that PGEO significantly protected against the increase of blood glucose induced by alloxan treatment. In addition, we showed that sub-acute essential oil treatment induced a decrease of lipoperoxydation, as well as, the induction of antioxidant enzyme activities. The use of GC-MS technique revealed the identification of many compounds in PGEO with (R)-citronellol (31.61%) as the main compound. The protective effect of PGEO is mainly attributed to antioxidant property.

Editorial: New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond.

Editorial: New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond.

Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management.

This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented TGF-β1/Smad3 signaling pathway

Context: Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN). Objective: This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN. Methods: Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p.o.). After 12 weeks, diabetic nephropathy biomarkers were assessed. The mRNA expression of collage I and III, TGF-β1 and Smad3 and were detected by RT–PCR. Results: Fenofibrate reduced significantly serum creatinine, kidney/body weight ratio, serum albumin excretion Collage I & III, TGF-β1 and Smad3 mRNA expression. Conclusions: Our results give further insights into the mechanisms underlying the protective role of fenofibrate in DN, suggesting that interference with TGF-β1/Smad3 signaling pathway may be a useful therapeutic approach to prevent DN.

Modulation of Diabetes-Induced Oxidative Stress, Apoptosis, and Ca2+ Entry Through TRPM2 and TRPV1 Channels in Dorsal Root Ganglion and Hippocampus of Diabetic Rats by Melatonin and Selenium

Neuropathic pain and hippocampal injury can arise from the overload of diabetes-induced calcium ion (Ca2+) entry and oxidative stress. The transient receptor potential (TRP) melastatin 2 (TRPM2) and TRP vanilloid type 1 (TRPV1) are expressed in sensory neurons and hippocampus. Moreover, activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death. Melatonin (MEL) and selenium (Se) have been considered potent antioxidants that detoxify a variety of reactive oxygen species (ROS) in neurological diseases. In order to better characterize the actions of MEL and Se in diabetes-induced peripheral pain and hippocampal injury through modulation of TRPM2 and TRPV1, we tested the effects of MEL and Se on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion (DRG) neurons of streptozotocin (STZ)-induced diabetic rats. Fifty-eight rats were divided into six groups. The first group was used as control. The second group was used as the diabetic group. The third and fourth groups received Se and MEL, respectively. Intraperitoneal Se and MEL were given to diabetic rats in the fifth and sixth groups. On the 14th day, hippocampal and DRG neuron samples were freshly taken from all animals. The neurons were stimulated with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We observed a modulator role of MEL and Se on intracellular free Ca2+ concentrations, current densities of TRPM2 and TRPV1 channels, apoptosis, caspase 3, caspase 9, mitochondrial depolarization, reduced glutathione, glutathione peroxidase, lipid peroxidation, and intracellular ROS production values in the neurons. In addition, procaspase 3 and 9 activities in western blot analyses of the brain cortex were also decreased by MEL and Se treatments. In conclusion, in our diabetes experimental model, TRPM2 and TRPV1 channels are involved in the Ca2+ entry-induced neuronal death and modulation of this channel activity by MEL and Se treatment may account for their neuroprotective activity against apoptosis and Ca2+ entry. Graphical Abstract Possible molecular pathways of involvement of melatonin and selenium in diabetes-induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus and DRG neurons of rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin and it is blocked by capsazepine (CPZ). Diabetes can result in augmented ROS release in hippocampal and DRG neurons through polyol reactions, leading to Ca2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca2+ provided intracellular Ca2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Melatonin and selenium reduce TRPM2 and TRPV1 channel activation through the modulation of polyol oxidative reactions and selenium-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model

Background: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. Methods: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. Results: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. Conclusion: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.

Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates.

This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

Expression of Vascular Endothelial Growth Factor Has a Regulatory Role in Gingival Venules in Experimental Diabetes.

In the present study, the possible localization and role of vascular endothelial growth factor receptor type 2 (VEGFR2) in the regulation of gingival venules in a rat model of experimental diabetes are examined. Six weeks after streptozotocin premedication, Wistar male rats presenting blood sugar levels >20 mmol/L were selected for investigation. The VEGFR2 antagonist ZM323881 [5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methylphenol-hydrochloride] (20 μg/mL) was dripped onto the gingiva between the mandibular incisors. Changes in diameter of the selected gingival venule were measured by vital microscopy combined with digital photography at specified times. Immunohistochemical staining was used to localize VEGFR2. For controls, the same protocol was used on animals with normal blood sugar levels and healthy gingiva. There was a significant difference between the baseline venule diameter of the diabetic and the control groups (47 ± 1 and 28 ± 2 μm, respectively). After 15, 30, and 60 minutes of local application of ZM323881, significant vasoconstriction was observed in the venules of diabetic rats compared with the baseline (81.4% ± 4.6%, 81.8% ± 4.4%, and 80.6% ± 5.1%, respectively). The control group showed no change in the venule diameter. The immunohistochemical analysis showed significantly increased VEGFR2 expression in the mast cells along the venules in the diabetic group, whereas mast cells were rarely found in the control group. The findings suggest that VEGF expression is increased in gingiva in experimentally induced diabetes. After VEGFR2 activation, the mast cell-derived vasodilatory and inflammatory mediators may contribute markedly to the concomitant changes in the microcirculation.

Conditioned Medium from Early-Outgrowth Bone Marrow Cells Is Retinal Protective in Experimental Model of Diabetes.

Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR.

An Update On Rodent Model Studies In Diabetic Neuropathy: A Brief Communication

The diseases of the peripheral nerves are quite common and diversified, are directly related to several factors, ranging from the imbalance related to good nutrition and adequate needs of nutrients, going to the injuries caused by drugs or mechanisms external to the human organism. Diabetes is a complex syndrome that affects and kills millions of people worldwide. We demonstrated through the experimental model of diabetes using STZ@ in single intraperitoneal dose of 60 mg / kg, that both a purely motor nerve can be directly affected as well as a special afferent nerve (cranial nerve), this comparison showed us that there is a possibility of having a new type of mixed type neuropathy, this may be related to the amount of the dose involved, such as the time of disease progression, but more studies need to be done for definitive confirmation. We can extrapolate the original results to understand the mechanisms of diabetes in humans, although it does not yet have an experimental model of type II diabetes, more related to eating disorders, the STZ application simulates the effects of type I or insulin dependent diabetes, with more serious and deleterious effects mainly the more distal portions of the nerves. Prevention and food control are very important, especially those related to the mechanisms that involve carbohydrate metabolism and its peripheral resistance. The original results commented here are relevant for the continuous study of this serious but old illness, but quite current in the medical and therapeutic clinic. Keywords: Experimental Model of Diabetes; Sensory and Motor Peripheral Nerves; Peripheral Nerve Injuries; Neuropathies; STZ; Rats.

The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

Background:Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus.Methods:The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms.Results:Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes.Conclusions:Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

Effects of crocin on experimental obesity and type-2 diabetes.

The aim of this study is to scrutinize the effects of crocin on obesity and type-2 diabetes, with an approach that takes oxidative stress and inflammatory parameters into account. The experimental obesity model was created by utilizing a 10-week-long high-fat diet (HFD). An experimental type-2 diabetes model was created by injecting multiple low-dose streptozocin (STZ) injections into rats that were fed with the HFD. The treatment groups were administered a daily crocin dose of 150 mg/kg for 6 weeks via gavage. Findings of the study demonstrated that crocin could be effective in relieving the symptoms of obesity and diabetes (hyperinsulinemia, hyperleptinemia, insulin resistance, and weight gain). It was determined that crocin lowered the plasma TNF-α and IL-1β levels and the pancreas tissue TNF-α and IFN-γ levels, which were increased due to diabetes, and reduced the inflammation in diabetic rats. Similarly, it was found that oxidative stress, which increased due to the progress of diabetes, was reduced in crocin treatment group. Crocin could contribute to the development of phytotherapeutic approaches in the treatment of obesity, diabetes, and diabesity (obesity-induced diabetes), which is promising as the abovementioned incidences have increased considerably in today's world.

Proteasome Activators, PA28αand PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN) and Monocyte Chemoattractant Protein-1 (MCP-1) in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO) mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR.

SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc.

Experimental model of mild diabetes: long-term evaluation of glycemic profile and gastric contractility in rats

Materials and methods Male Wistar rats were divided into mild diabetes (n=14) and control (n=8) groups. For mild diabetes induction, newborn rats received streptozotocin (STZ-100 mg/kg, subcutaneously) in a citrate buffer and control animals received only citrate buffer on the first day of life. The oral glucose tolerance test (OGTT) was performed three months later and blood glucose was measured monthly by glucometer Facil True Read (Home Diagnostics). The gastric contractility was evaluated by Alternate Current Biosusceptometry (ACB), a previously validated and noninvasive biomagnetic technique. After 12 h fasting, the animals were fed with 2g of magnetically marked chow and anesthetized with sodium pentobarbital (40 mg/kg, intraperitoneally). All rats were placed in a supine position with ACB sensor positioned on the gastric region during 30 min. Frequency and amplitude of gastric contractions, also abnormal rhythmic index, were obtained from signals. Comparisons were performed by ANOVA (Tukey), being significant at p<0.05. OGTT confirmed diabetes in the STZ-induced group, demonstrating the success of the model.

Study of hypoglycemic activity of tablets of “Gliphasonorm” capsules and “Gliphasolin” on the model of streptozotocin-induced diabetes in rats

&lt;p&gt;The conducted research allowed to determine that the tablets “Gliphasonorm” capsules and “Gliphasolin” in an&lt;br /&gt;experimental model of streptozotocin-induced diabetes significantly reduced the level of glycosylated hemoglobin,&lt;br /&gt;decreased with the level of glucose in the blood of animals compared to diabetic control. After 14 days of the study&lt;br /&gt;capsules “Gliphasolin” showed a more pronounced hypoglycemic activity (4.4 % and 8.0 % greater) than tablets&lt;br /&gt;“Gliphasonorm” and the reference drug metformin. Under the action caps “Gliphasolin” on the 12th day of the study&lt;br /&gt;showed marked reduction of glycosylated hemoglobin in the blood of animals (3.1 % and 5.6 % greater) than that of&lt;br /&gt;the tablets of “Gliphasonorm” and metformin. Capsules “Gliphasolin” and tablets “Gliphasonorm” based bioflavonoid&lt;br /&gt;complex from beans are promising in the therapy of diabetes type 2 on the background of obesity and reduce the&lt;br /&gt;risk of micro- and macroangiopathies.&lt;/p&gt;

Increased levels of adenosine and ecto 5′-nucleotidase (CD73) activity precede renal alterations in experimental diabetic rats

The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5’-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-β as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.

A novel carboxymethylated mercaptotriazinoindole inhibitor of aldose reductase interferes with the polyol pathway in streptozotocin-induced diabetic rats.

The aim of the present work was to study the effect of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo. In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by V(max) value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC(50) values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 microM CMTI was recorded (I=0.9+/-2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications.

Antidiabetic effect of honey feeding in noise induced hyperglycemic rat: involvement of oxidative stress.

In this study the effect of oral administration of honey on serum glucose, lipids, stress oxidative markers, and morphology of langerhans islets in noise induced hyperglycemic rats was investigated. Male Wistar rats were divided into control, hyperglycemic, honey treated control, and honey treated hyperglycemic groups. For induction of hyperglycemia, noise stress was used. Serum glucose, triglyceride (TG), total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL)-cholesterol levels were determined before the study and at 4(th) and 8(th) weeks after the study. Markers of oxidative stress in brain were also measured. Morphology of langerhans islets in four groups was evaluated using Gomori staining method. Treatment of noise induced hyperglycemic rats with honey produced a hypoglycemic effect and appropriate changes regarding serum lipids in treated diabetic group at 4(th) and 8(th) weeks as compared to the control group. Meanwhile, honey treatment significantly ameliorated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in brain. Histology of langerhans islets in hyperglycemic group showed a lower number and granularity of beta cells; honey treatment produced beneficial change in this respect. Oral administration of honey in experimental model of diabetes showed a significant hypoglycemic effect and led to appropriate changes in serum lipid profiles.

Neonatal streptozotocin-induced diabetes in mothers promotes metabolic programming of adipose tissue in male rat offspring.

Maternal hyperglycemia during pregnancy can lead to fetal changes, like macrosomia or obesity in adultlife. Experimentalmodels of diabetes have been studied to evaluate the consequences of offspring lipidmetabolism. This study aimed to investigate the metabolic changes in adipose tissue of offspring of streptozotocininduced diabetic mothers during neonatal period. Diabetes was induced in female rats by streptozotocin administration on 5th day of life. In adulthood, female rats were bred with control male rats. Male puppies were sacrificed on 12th week of life and epididymal (EP) and subcutaneous (SC) adipose fat pads were excised and weighted. Adipocytes were isolated and evaluated for basal and insulin-stimulated 2-deoxyglucose uptake, oxidation of glucose into CO2, and incorporationof glucose into lipids and lipolytic capacity. Bodyweight, EP fat padweight and diameter of adipocytes fromoffspring of diabeticmothers were increased in comparison to offspring of control mothers. EP adipocytes from offspring of diabetic mothers presented increased basal and insulin stimulated glucose uptake in comparison to control ones. Similar pattern was observed for glucose oxidation into CO2 and incorporation into lipids. However, significant difference in lipolytic capacity in vitrowas not observed. Protein content of GLUT4, insulin receptor and acetyl-CoA carboxylase was significantly increased in EP fat pad of offspring of diabetic mothers in relation to control group. Metabolic programming occurred in the adipose tissue of offspring of diabetic mothers, increasing its capacity to store lipids with no changes in lipolytic capacity.