Streptozotocin-induced Diabetic Male Wistar Rats Research Articles

Anti-diabetic activity of aqueous extract of Trichilia prieureana A. Juss leaves in fructose-fed streptozotocin-induced diabetic male Wistar rats

Background and aimEthanolic extract of Trichilia prieureana leaves have been reported to exhibit anti-hyperglycemic activities without detailed information on the anti-diabetic activities. This study investigated the anti-diabetic activity of aqueous extract of T. prieureana leaves (AETPL) in type 2 diabetic (T2DM) male rats. Experimental procedureT2DM rats (induced with 10 % fructose solution ad libitum for 2 weeks and streptozotocin [STZ]; 40 mg/kg body weight {BW}) in groups B, C, D, E, and F were also administered distilled water (DW), metformin (100 mg/kg BW), 11.2, 22.3, and 44.6 mg/kg BW of AETPL, respectively, whilst non-diabetic rats in Group A received DW only (Sham Control, SC) for 14 days. The T2DM-related parameters were then evaluated. ResultsThe fructose-fed streptozotocin-(FSTZ) treatment related significant (p < 0.05) increases in FBS, HbA1c, fructosamine, HOMA-IR, G6P, GP, TC, TG, LDL-C, urea, bilirubin, hepatic and pancreatic MDA levels; decreases in BW, serum insulin, creatinine, albumin, HOMA-β, glycogen, G6PD, HK, HDL-C, hepatic and pancreatic SOD, GPX, RG, catalase, Hb, PCV, MCH, MCHC, MCV, RBC, WBC, differentials and the destruction of the pancreatic β-cells, hepatocyte degeneration, and central hepatic vein congestion were reversed by AETPL, to values that compared well with SC in most cases. In the IpGGT model, the intraperitoneally administered AETPL reduced the blood glucose and elevated the plasma insulin levels. The AETPL at 44.6 mg/kg BW exhibited the most pronounced effects. ConclusionAETPL (44.6 mg/kg BW) restored T2DM-glycemic control and associated biochemical changes via up-regulation of insulin, carbohydrate metabolizing enzymes and restoration of pancreatic and hepatic histoarchitecture.

Ethanol leaf extract of Alchornea cordifolia (Euphorbiaceae) effects on reproductive dysfunctions in streptozotocin-induced diabetic male Wistar rats

Abstract. Ejeh SA, Abu HA, Onyeyili PA, Abenga JN, Abalaka SE, Enefe NG, Eugiene I. 2024. Ethanol leaf extract of Alchornea cordifolia (Euphorbiaceae) effects on reproductive dysfunctions in streptozotocin-induced diabetic male Wistar rats. Asian J Nat Prod Biochem 22: 35-42. Diabetes and some of its treatment agents reportedly induce male reproductive dysfunction in male Wistar rats. Therefore, the study investigated the therapeutic effects of ethanol leaf extract of Alchornea cordifolia (Schumach. &amp; Thonn.) Müll. Arg. on diabetic male Wistar rats. Twenty-five male Wistar rats were used, and 50 mg/kg freshly prepared streptozotocin in cool citrate buffer single intraperitoneal injection was used to induce diabetes mellitus. The rats were grouped into 5 of 5 rats each. Group 1 was normal + distilled water; group II was diabetic untreated; group III was diabetic + 100 mg/kg metformin HCl; and IV and V rats were diabetic and received 100 and 200 mg/kg of the extract orally, respectively. Treatment was done for 28 days; after that, reproductive parameters such as extrapyramidal sperm parameters (sperm motility, count, concentrations, viability, morphology, and acrosome integrity) and hormonal assay (FSH, LH, and Testosterone) were evaluated using a standard protocol. Testicular and epididymal histopathological changes were analyzed using standard procedure. The results revealed a marked impairment in all the parameters evaluated in the untreated diabetic group. However, groups exposed to the ethanol leaf extract of A. cordifolia recorded a significant (p &lt;0.05) improvement in the above-mentioned reproductive parameters, including the restorations of the collapsed epididymal tubules observed in the diabetic untreated group. Therefore, the ethanol leaf extract of A. cordifolia can potentially facilitate and restore reproductive dysfunctions associated with diabetes mellitus complications, hence a possible alternative to synthetic antidiabetic agents.

Diet Supplementation with Rosemary (Rosmarinus officinalis L.) Leaf Powder Exhibits an Antidiabetic Property in Streptozotocin-Induced Diabetic Male Wistar Rats

Diabetes mellitus is a metabolic disorder that has a high global health burden and causes high mortality and morbidity in humans. Medicinal herbs and plants offer a promising alternative to conventional therapies for the management of diabetes. Rosemary (Rosmarinus officinalis L.) is a traditional medicinal herb that has been used for the management of several diseases. Therefore, the present study investigates the antidiabetic properties of diets supplemented with R. officinalis leaf powder on streptozotocin-induced diabetic Wistar rats. First, the phytochemicals and 2,2-dephenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity of aqueous R. officinalis leaf extract were determined. Streptozotocin-induced diabetic male Wistar rats were fed a diet supplemented with R. officinalis leaf powder (ROP) at 3%, 6%, and 12%, respectively, for 6 weeks. Investigations of food intake, body weight, rat relative organ weights, blood glucose, lipid profiles, creatinine, bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were estimated according to standard procedures. The results show that ROP aqueous extract contains significant amounts of phenolics, flavonoids, and tannins, which exhibit in vitro DPPH free-radical scavenging activity. Based on an in vivo study, ROP reduced blood glucose levels in streptozotocin-induced diabetic animals (p &lt; 0.05). Dietary supplementation with ROP in diabetic rats significantly (p &lt; 0.05) lowered ALT, AST, bilirubin, creatinine, total triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels while increasing high-density lipoproteins (HDLs) when compared with the diabetic control group. Our findings demonstrate that a diet supplemented with R. officinalis leaf powder exhibits an antidiabetic potential with improved health outcomes, as demonstrated by the improved lipid and liver profile enzymes in our animal model.

Pancreatic beta cell regenerative potential of Zanthoxylum chalybeum Engl. Aqueous stem bark extract

Ethnopharmacological relevanceZanthoxylum chalybeum Engl. is endemic to Africa and has been used traditionally to treat diabetes mellitus. Moreover, its pharmacological efficacy has been confirmed experimentally using in vitro and in vivo models of diabetes. However, the effects of Z. chalybeum extracts and its major constituent compounds on beta cell and islet regeneration are not clear. Further, the mechanisms associated with observed antidiabetic effects at the beta cell level are not fully elucidated. Aim of the studyWe determined the beta cell regenerative efficacy of Z. chalybeum aqueous stem bark extract, identified the chemical compounds in Z. chalybeum aqueous stem bark extracts and explored their putative mechanisms of action. Materials and methodsPhytochemical profiling of the Z. chalybeum extract was achieved using ultra high-performance liquid chromatography hyphenated to high-resolution mass spectrometry. Thereafter, molecular interactions of the compounds with beta cell regeneration targets were evaluated via molecular docking. In vitro, effects of the extract on cell viability, proliferation, apoptosis and oxidative stress were investigated in RIN-5F beta cells exposed to palmitate or streptozotocin. In vivo, pancreas tissue sections from streptozotocin-induced diabetic male Wistar rats treated with Z. chalybeum extract were stained for insulin, glucagon, pancreatic duodenal homeobox protein 1 (Pdx-1) and Ki-67. ResultsBased on ligand target and molecular docking interactions diosmin was identified as a dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) inhibitor. In vitro, Z. chalybeum augmented cell viability and cell proliferation while in palmitate-pre-treated cells, the extract significantly increased cell activity after 72 h. In vivo, although morphometric analysis showed decreased islet and beta cell size and density, observation of increased Pdx-1 and Ki-67 immunoreactivity in extract-treated islets suggests that Z. chalybeum extract has mild beta cell regenerative potential mediated by increased cell proliferation. ConclusionsOverall, the mitogenic effects observed in vitro, were not robust enough to elicit sufficient recovery of functional beta cell mass in our in vivo model, in the context of a sustained diabetic milieu. However, the identification of diosmin as a potential Dyrk1A inhibitor merits further inquiry into the attendant molecular interactions.

Ameliorative Potentials of Methanol Bark Extract of Detarium senegalense (Tallow Tree) in Streptozotocin Induced Diabetic Male Wistar Rats

Diabetes is a global metabolic disease that affects millions of individuals worldwide and raises the global death rate, posing a public health concern. Because antidiabetic traditional drugs are expensive, have side effects, and are ineffective, researchers are looking into novel medicinal plants to find a long-term cure that is inexpensive, has few or no side effects, and is highly effective in treating diabetes and its consequences. Detarium senegalense is a versatile plant used to cure a variety of ailments, including diabetes. This research aimed to investigate the ameliorative potentials of methanol bark extract of Detarium senegalense in streptozotocin-Induced Diabetic male Wistar Rats. Thirty (30) adult male Wistar rats weighing 120-180gm were chosen at random and put into six (6) groups of five rats each (n=5) for this investigation. A single intraperitoneal injection of streptozotocin (150mg/kg) produced diabetes in rats. Normal and diabetic control groups are represented by groups 1 and 2, respectively. Group 3, a diabetic group, received metformin (50mg/kg). Groups 4, 5, and 6 received methanol bark extract of Deterium senegalenses at 250, 500, and 1000 mg/kg/day, respectively. The animals were euthanized at the end of the 21-day treatment period, and organs were excised for biochemical examination. The generated data was analyzed with the SPSS software, and the results were expressed as mean SEM. Result confirms Detarium senegalense methanol bark extract as a hypoglycemic agent on the diabetic rats, by decreasing blood glucose level and the activity of metabolic enzymes (α-amylase and α-glucosidase), increase hexokinase, Superoxide dismutase, Catalase, Glut 1 and Glut 2 activities while decreasing the activities of Malondialdehyde. Conclusively, the bark of Detarium senegalense has been shown to have anti-diabetic and anti-oxidative.

Influence of lauric acid on the relaxation of corpus cavernosum in streptozotocin-induced diabetic male Wistar rats

BackgroundDiabetes mellitus is a global health challenge and has been recognised as a risk factor for erectile dysfunction. Dissatisfaction with standard medications has been reported by some patients, hence therapeutic plants are being considered as a viable alternative therapy, with their active components being investigated to create a standard regimen. Lauric acid is the most abundant constituent of coconut oil and is proposed to be responsible for its therapeutic properties. The corpus cavernosum plays an important role in erectile function with its relaxation favouring erection. This study thus sought to investigate the possible relaxant action and mechanism of lauric acid on the corpus cavernosum of diabetic male Wistar rats. Diabetes was induced by intraperitoneal injection of streptozotocin after which graded doses of lauric acid were administered orally to three groups of diabetic rats, once daily for 4 weeks. At the end of the experiment, the corpus cavernosal tissues of the rat penis were extracted. Following phenylephrine or potassium chloride (KCl)—induced contraction, relaxation response to acetylcholine and sodium nitroprusside was used to evaluate endothelium-dependent and nitric oxide-mediated relaxation, respectively.ResultsRelaxation response to acetylcholine, following pre-contraction with phenylephrine, was significantly decreased in the cavernosal tissues of diabetic untreated rats and was not significantly improved in lauric acid treated diabetic groups. Relaxation response to acetylcholine, following pre-contraction with KCl, was significantly decreased in the diabetic untreated group but was significantly improved in lauric acid treated diabetic groups at the lowest dose. Decreased relaxation response to sodium nitroprusside, following pre-contraction with phenylephrine in tissues of diabetic untreated rats, was significantly improved in lauric acid-treated diabetic groups at lower doses. Decreased relaxation response to sodium nitroprusside, following pre-contraction with KCl, was significantly improved in lauric acid-treated diabetic groups at all doses.ConclusionLauric acid improved relaxation of corpus cavernosum muscle in diabetic male rats by enhancing nitric oxide-mediated relaxing action of sodium nitroprusside and possibly inhibiting KCl-induced contraction.

The Role of an Aqueous Extract of Cactus on Histopancreatic Architecture in Streptozotocin Induced Diabetes Mellitus in Wistar Rats

Herbs have been used as medicinal for several years to cure or rather manage different ailments such as diabetes mellitus. This is very common in rural settings of sub-saharan Africa and is now being adopted in urban areas. Opunta species have widely been seen to contain antihyperglycaemic effects. To evaluate the antihyperglycaemic and histopancreatic effect of aqueous extract of prickly pear cactus (Opuntia species) cladodes in streptozotocin-induced diabetic male Wistar rats in vivo. This was a laboratory based research conducted at Mulungushi University involving 30 wistar rats (Rattus norvegicus) that weighed between 160-200 g which were randomly selected into five groups (6 per cage); normal control, diabetic control, diabetic +metformin, diabetic +cactus and cactus only group. Initial blood glucose levels were obtained from the tail and record then Diabetes mellitus was induced using a single intraperitoneal dose of streptozotocin (70mg/kg BW) and established a persistent state of hyperglycemia after 72hours. The aqueous cactus extract of 100 mg/kg BW and metformin of 100 mg/kg BW was administered orally using intragastric cannula daily for a period of 4 weeks. At the end of the fourth week, Diabetes + cactus and diabetes + metformin groups body weights were statistically significant when compared to the diabetic group (P&lt;0.05). While diabetic group was statistically significant when compared to normal control (P&lt;0.05). The relative weight of the pancreas in diabetic group was statistically significant to other groups (P&lt;0.05). The blood glucose in diabetic + cactus was normoglycaemic at 3rd week, Diabetic + metformin group when compared to diabetic group was statistically significant (P&lt;0.05). The normal control and cactus only groups maintained normoglycaemic till the end of the 4th week. The histological findings of the normal control and cactus only group showed normal pancreatic cytoarchitecture. Diabetes group showed high degree of disorganization in the cytoarchitecture in the islet with reduction in β cell mass and deposition of elastic fibres. The Diabetic+Metformin group showed slight decrease in the cell mass (β cells) and elastic fibres were extensively deposited. Diabetic+Cactus treated group exhibited normal histology of the pancreas with increased number of β cells. Opuntia species are able to lower elevated blood glucose levels and ameliorate the effects of STZ on the pancreatic morphology

Methanolic Leaf Extract of Dryopteris dilatata Reverses Kidney Injury on Streptozotocin-Induced Diabetic Male Wistar Rats

Background: Hyperglycemia when sustained leads to diabetes which has become a chronic disorder having morbidity and mortality rate. This study investigated the effect of methanolic leaf extract of Dryoptersis dilatata (MEDd) on kidney injury caused on streptozotocin (STZ)-induced diabetic Wistar rats. Materials and Methods: Thirty Wistar rats were divided into five groups of six rats each. Group 1 received distilled water (10 ml/kg); Group 2 received STZ (60 mg/kg) only, Groups 3 and 4 received STZ followed by 400 and 800 mg/kg of MEDd, respectively, while Group 5 received STZ + Pioglitazone (10 mg/kg). After 2 weeks of treatment, rats were sacrificed and blood, spleen, liver, pancreas, and kidney were collected for biochemical analysis. Results: The results showed that MEDd extract caused a significant decrease (P &lt; 0.05) in STZ-induced diabetic rats, oxidative stress markers, malondialdehyde nitric oxide, and glutathione superoxide were ameliorated in organs such as the kidney and pancreas in diabetic rats after treatment with MEDd. Kidney markers (urea and creatinine) were ameliorated as well as reduction in organ weights in diabetic rats following treatment with MEDd. Conclusion: Therefore, it was observed from our study that MEDd has antidiabetic and nephron-protective capacity as it ameliorates in vivo adopted in lieu of nephropancreatic caused by STZ-induced diabetes.

Ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats

Hyperglycemia is a central trait of diabetes mellitus (DM) and is linked to an increase in free radical generation and oxidative stress in the testes, resulting in testicular tissue damage and male infertility. Synthetic medicines are commonly used to manage diabetes; however, they are costly and associated with adverse effects. As a result, the search for a safer and affordable alternative from medicinal plants that contain antioxidants has become imperative to scavenge free radicals caused by hyperglycaemia, thereby alleviating male reproductive dysfunction. Therefore, the present aimed to investigate the ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats. A total of 64 male Wistar rats (eight weeks old) weighing 180 ± 10 mg/kg were divided into seven groups at random. Type 2 diabetic mellitus (T2DM) was induced by streptozotocin (STZ) and a 10% fructose injection intraperitoneally using 40 mg/kg body weight rats. The levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, and ferric reducing antioxidant (FRAP) as well as 2, 2-diphenyl-1-picrylhydrazyl (DPPH) values were used to establish the testicular oxidative status. It was found thatA.difformisextract significantly (p < 0.05) lowered MDA levels in diabetic rats. Both CAT and SOD activity were significantly (p < 0.05) lower following induction of DM and increased (p < 0.05) after treating withA. difformis. The findings of this study show that A. difformis extract could be a promising source of lead compounds for the development of a therapeutic agent to treat male infertility caused by DM complications.

Effect of Momordica charantia on Insulin Immune-reactive Pancreatic Beta Cells and Blood Glucose Levels in Streptozotocin-induced Diabetic Rats

The present study was conducted to determine the antidiabetic effect of Momordica charantia on pancreatic islets of Langerhans in streptozotocin-induced diabetic male Wistar rats in relation to the distribution of insulin immuno-positive beta cells. Momordica charantia was fed to rats at 2 %, 5 % and 10 % of the standard diet for 12 w. After sacrifice, the pancreatic tissues were obtained for histopathological and immunohistochemical observations. In addition, monitoring of fasting blood glucose was applied each month during experimental period. The results revealed that the oral doses of Momordica charantia at 5 % and 10 % of the daily diet increased the percentage of insulin-positive pancreatic beta cells as well as the size and number of pancreatic islets. Moreover, significant (p≤0.01) dose and time-dependent reduction in fasting blood glucose levels were observed. In conclusion, these results suggest that Momordica charantia induces antidiabetic effects via regeneration of insulin-positive pancreatic beta cells and increase the number of insulin secretory granules; hence, blood glucose reduction.

Effects of Psidium guajava ethanolic leaf extract on epidermal wound healing in streptozotocin-induced diabetic male Wistar rats

Diabetes mellitus (DM) occurrence is increasing. Canine DM is multifactorial and global prevalence is 0.005 to 1.5% affecting both sexes between 4-14 years old. Diabetic foot ulcer is a complication of DM impairing wound healing. Psidium guajava (PG) is a food and medicinal plant containing quercetin (a potent antioxidant) in its leaf and used in locally to manage DM. Effects of ethanolic extract of PG leaves on in vivo animal diabetic models have not been investigated indeptly with little documented information on the effect of PG extract on wound management in diabetics. This study evaluated the beneficial role of PG ethanolic leaf extract (PGELE) in an experimental model of diabetes-related wound healing disorders. Ethanolic extracts were prepared from PG leaves. Thirty male Wistar rats (190-205 g) were separated into 6 groups (n = 5) and treated for 2 weeks. Group I (control), II (streptozotocin 60 mg/kg once), III &amp; IV (streptozotocin 60 mg/kg once, PGELE (125 &amp; 250 mg/kg rat/day) per os), V (streptozotocin 60 mg/kg once, glibenclamide 5 mg/kg b.w) and VI (PGELE 250 mg/kg orally). Plasma glucose was determined by glucometer. 10 x 10 mm wounds were made under anaesthesia. Full blood count was done by microscopy. Data were analysed using ANOVA at α0.05. Glucose concentration was significantly higher in II (583 ± 4.16 mg/dL) compared to others. Wound contraction rates were significantly slower in II (41 ± 0.23 %) compared to others. There was no difference in haematology. PGELE improved wound healing in streptozotocin-induced diabetic Wistar rats.

The Effect of High Dietary Salt Consumption on Renal Function in Streptozotocin-Induced Diabetic Male Wistar Rats

The Effect of High Dietary Salt Consumption on Renal Function in Streptozotocin-Induced Diabetic Male Wistar Rats

Effect of hyperglycemia on fertility in streptozotocin-induced diabetic male Wistar rats: focus on glucose transporters and oxidative stress

BACKGROUND Glucose transporters (GLUTs) and oxidant metabolism are associated with the mechanism of infertility. This study evaluated the impact of hyperglycemia on glucose and oxidant metabolisms of Sertoli cells (SCs).&#x0D; METHODS This study was an animal study to investigate the expression of messenger RNA monocarboxylate transporter 4 (MCT4), GLUT1, GLUT3, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase, catalase (CAT), and lactate dehydrogenase A (LDHA) of Wistar rats testes that were induced hyperglycemia. Reverse transcription polymerase chain reaction analysis was used. Hyperglycemic state in the Wistar rats was induced by streptozotocin. 24 rats were divided into 3 groups: non-hyperglycemia (control), 2-week, and 4-week hyperglycemic state. All data were collected and analyzed using SPSS version 15.0 (IBM Corp., USA).&#x0D; RESULTS The expression of glucose transporter (GLUT1 and GLUT3), lactate transporter (MCT4), and cellular defense protein against oxidant (Nrf2 and CAT) was significantly increased in the 2-week and 4-week hyperglycemic state groups with p&lt;0.01, respectively.&#x0D; CONCLUSIONS Hyperglycemic state affects the metabolism of SCs. Alteration of GLUTs and oxidative metabolism may indicate metabolic alterations by a prolonged exposure to hyperglycemia that may be responsible for diabetes-related male infertility.

Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model

Hyperglycemia mediated perturbations in biochemical pathways induce angiogenesis in diabetic retinopathy (DR) pathogenesis. The present study aimed to investigate the protective effects of lactucaxanthin, a predominant lettuce carotenoid, on hyperglycemia-mediated activation of angiogenesis in vitro and in vivo diabetic model. ARPE-19 cells cultured in 30 mM glucose concentration were treated with lactucaxanthin (5 μM and 10 μM) for 48 h. They were assessed for antioxidant enzyme activity, mitochondrial membrane potential, reactive oxygen species, and cell migration. In the animal experiment, streptozotocin-induced diabetic male Wistar rats were gavaged with lactucaxanthin (200 μM) for 8 weeks. Parameters like animal weight gain, feed intake, water intake, urine output, and fasting blood glucose level were monitored. In both models, lutein-treated groups were considered as a positive control. Hyperglycemia-mediated angiogenic marker expressions in ARPE-19 and retina of diabetic rats were quantified through the western blot technique. Expression of hypoxia, endoplasmic reticulum stress markers, and vascular endothelial growth factor were found to be augmented in the hyperglycemia group compared to control (P < 0.05). Hyperglycemia plays a crucial role in increasing cellular migration and reactive oxygen species besides disrupting tight junction protein. Compared to lutein, lactucaxanthin aids retinal pigment epithelium (RPE) function from hyperglycemia-induced stress conditions via downregulating angiogenesis markers expression. Lactucaxanthin potentiality observed in protecting tight junction protein expression via modulating reactive oxygen species found to conserve RPE integrity. Results demonstrate that lactucaxanthin exhibits robust anti-angiogenic activity for the first time and, therefore, would be useful as an alternative therapy to prevent or delay DR progression.

α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys.

α-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-β1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.

High dietary salt intake alleviates fasting blood glucose in streptozotocin-induced diabetic male Wistar rats

High dietary salt intake alleviates fasting blood glucose in streptozotocin-induced diabetic male Wistar rats

Exogenous Ghrelin Increases Plasma Insulin Level in Diabetic Rats.

Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24–51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10−6 M and 10−12 M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.

Aqueous extract of Digitaria exilis grains ameliorate diabetes in streptozotocin-induced diabetic male Wistar rats

The absence of scientific data on the age long folkloric use of Digitaria exilis grains by sufferers of diabetes prompted the present investigation. This study was aimed at evaluating the antidiabetic activity of aqueous extract of Digitaria exilis grains in streptozotocin (STZ)-induced diabetic rats. Forty two male rats (166.43 ± 3.32 g) were completely randomized into six groups (A-F) of 7 animals each. Animals in group A (control) were administered 0.5 ml of distilled water while those in groups B, C, D, E and F which were induced with diabetes mellitus (by intraperitoneal administration of 60 mg/kg body weight of STZ) were also administered distilled water, 50 mg/kg body weight of metformin (a reference antidiabetic drug), 50, 100 and 200 mg/kg body weight of aqueous extract of D. exilis grains respectively, twice daily for 14 days. Blood glucose levels and some relevant biomolecules were determined 14 days post-administration. Alkaloids, flavonoids, saponins, tannins, anthraquinones, terpenoids, cardiac glycosides, phlobatannins, phenolics and cardenolides were detected in the extract with alkaloids (30.20 mg/ml) occurring the most and phlobatannins (0.22 mg/ml) the least. Streptozotocin significantly (p < 0.05) increased the levels of blood glucose, serum albumin, urea, creatinine and cholesterol, activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver and intake of feed and water. Body weight, weight of pancreas, pancreatic insulin, liver glycogen content, red blood cell and white blood cell and their related indices, liver hexokinase and phosphofructokinase activities were significantly reduced by STZ. In contrast, the extract significantly reversed all those STZ-treatment induced changes with the 200 mg/kg body weight of the extract producing profound values that compared favourably with the distilled water treated non-diabetic animals and metformin treated diabetic animals. Overall, this study revealed that Digitaria exilis grains possess antidiabetic activity via increased insulin secretion, as plasma concentrations of insulin were not determined, enhanced activities of hexokinase and phosphofuctokinase and repletion of hepatic glycogen content.

Chronic administration of nano-sized PAMAM dendrimers in vivo inhibits EGFR-ERK1/2-ROCK signaling pathway and attenuates diabetes-induced vascular remodeling and dysfunction

We investigated whether chronic administration of nano-sized polyamidoamine (PAMAM) dendrimers can have beneficial effects on diabetes-induced vascular dysfunction by inhibiting the epidermal growth factor receptor (EGFR)-ERK1/2-Rho kinase (ROCK)—a pathway known to be critical in the development of diabetic vascular complications. Daily administration of naked PAMAMs for up to 4 weeks to streptozotocin-induced diabetic male Wistar rats inhibited EGFR-ERK1/2-ROCK signaling and improved diabetes-induced vascular remodeling and dysfunction in a dose, generation (G6 > G5) and surface chemistry-dependent manner (cationic > anionic > neutral). PAMAMs, AG1478 (a selective EGFR inhibitor), or anti-EGFR siRNA also inhibited vascular EGFR-ERK1/2-ROCK signaling in vitro. These data showed that naked PAMAM dendrimers have the propensity to modulate key (e.g. EGFR) cell signaling cascades with associated pharmacological consequences in vivo that are dependent on their physicochemical properties. Thus, PAMAMs, alone or in combination with vasculoprotective agents, may have a beneficial role in the potential treatment of diabetes-induced vascular complications.

Effects of short- and long-term regular exercise on reproductive tissue in streptozotocin-induced diabetic male Wistar rats.

Reproductive disorders are one of the complications of diabetes mellitus. Since conflicting results have been obtained from different studies, which examined serum levels of cytokines in patients with diabetes, and considering the fact that the origin of cytokines cannot be accurately determined from their serum changes, attempts were made in the present study to study histological changes and testicular tissue levels of TNF-α and IL-1 in rats treated with exercise. Considering the effects of exercise in reducing blood sugar level and its complications, two types of short-term and long-term regular exercises were also considered to evaluate their effects on male reproductive tissues. In this study, 60 male rats with the weight range of 250±50 g were used and were randomly divided into six groups (10 rats each). Healthy groups included sedentary control group, and groups treated with two and eight weeks of exercise. Rats with type 1 diabetes (induced by streptozotocin) included sedentary control group, groups treated with two and eight weeks of exercise (six groups). All groups were evaluated in terms of testicular tissue levels of TNF-α and IL-1 using ELISA and the histometry of spermatogonia, primary spermatocytes, Sertoli cells, epithelial thickness, diameter of veins, and thickness of the seminiferous tubule. Histological changes resulting from diabetes, particularly in the diameter of testicular veins and a number of cells, including Sertoli, highlights the important fact that tissue perfusion in patients with diabetes is especially crucial, in a way that exercise proved useful for tissue structures by offsetting this complication. Measurement of the cytokines IL-1 and TNF-α in the current study showed that perfusion problems are more important in diabetic complications than inflammatory factors. The main result of this research is recommendation of investigating the tissue of interest for diagnosis of diabetes complications, measuring inflammatory mediators of tissue rather than evaluating their serum concentrations, and focusing on vascular complications as a major complication of diabetes. Furthermore, regular exercise could help improve the function of reproductive organs in healthy groups and prevent diabetes infertility complications to an acceptable degree in diabetic groups.