Displaying publications 121 - 140 of 252 in total

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  1. Machha A, Achike FI, Mustafa AM, Mustafa MR
    Nitric Oxide, 2007 Jun;16(4):442-7.
    PMID: 17513143 DOI: 10.1016/j.niox.2007.04.001
    The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/enzymology
  2. Lee YF, Sim XY, Teh YH, Ismail MN, Greimel P, Murugaiyah V, et al.
    Biotechnol Appl Biochem, 2021 Oct;68(5):1014-1026.
    PMID: 32931602 DOI: 10.1002/bab.2021
    High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC- and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy; Diabetes Mellitus, Experimental/metabolism*; Diabetes Mellitus, Experimental/urine
  3. Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S
    Int J Mol Sci, 2011;12(3):1888-907.
    PMID: 21673929 DOI: 10.3390/ijms12031888
    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/metabolism*; Diabetes Mellitus, Experimental/prevention & control
  4. Wee CL, Mokhtar SS, Singh KKB, Yahaya S, Leung SWS, Rasool AHG
    Oxid Med Cell Longev, 2021;2021:3109294.
    PMID: 33623633 DOI: 10.1155/2021/3109294
    Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.
    Matched MeSH terms: Diabetes Mellitus, Experimental/complications; Diabetes Mellitus, Experimental/enzymology*; Diabetes Mellitus, Experimental/pathology
  5. Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
    PMID: 33047165 DOI: 10.1007/s00210-020-01989-w
    Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology
  6. Dehghan F, Hajiaghaalipour F, Yusof A, Muniandy S, Hosseini SA, Heydari S, et al.
    Sci Rep, 2016 Apr 28;6:25139.
    PMID: 27122001 DOI: 10.1038/srep25139
    Saffron is consumed as food and medicine to treat several illnesses. This study elucidates the saffron effectiveness on diabetic parameters in-vitro and combined with resistance exercise in-vivo. The antioxidant properties of saffron was examined. Insulin secretion and glucose uptake were examined by cultured RIN-5F and L6 myotubes cells. The expressions of GLUT2, GLUT4, and AMPKα were determined by Western blot. Diabetic and non-diabetic male rats were divided into: control, training, extract treatment, training + extract treatment and metformin. The exercise and 40 mg/kg/day saffron treatments were carried out for six weeks. The antioxidant capacity of saffron was higher compare to positive control (P  0.05). Serum glucose, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, insulin resistance, and glycated hemoglobin levels decreased in treated rats compared to untreated (p  0.05). The findings suggest that saffron consuming alongside exercise could improve diabetic parameters through redox-mediated mechanisms and GLUT4/AMPK pathway to entrap glucose uptake.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/metabolism; Diabetes Mellitus, Experimental/therapy*
  7. Al-Zuaidy MH, Mumtaz MW, Hamid AA, Ismail A, Mohamed S, Razis AFA
    BMC Complement Altern Med, 2017 Jul 10;17(1):359.
    PMID: 28693595 DOI: 10.1186/s12906-017-1849-2
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract.

    METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.

    RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.

    CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/etiology
  8. Mohamed EA, Ahmad M, Ang LF, Asmawi MZ, Yam MF
    PMID: 26649063 DOI: 10.1155/2015/754931
    In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3'hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  9. Al-Bayaty F, Abdulla MA
    PMID: 22666291 DOI: 10.1155/2012/468764
    Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  10. Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH
    PMID: 24204387 DOI: 10.1155/2013/102901
    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  11. Cheng PG, Phan CW, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR
    PMID: 24348715 DOI: 10.1155/2013/671252
    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  12. Giribabu N, Eswar Kumar K, Swapna Rekha S, Muniandy S, Salleh N
    PMID: 25852767 DOI: 10.1155/2015/542026
    The effect of V. vinifera seeds on carbohydrate metabolizing enzymes and other enzymes of the liver in diabetes is currently unknown. We therefore investigated changes in the activity levels of these enzymes following V. vinifera seed extract administration to diabetic rats. Methods. V. vinifera seed ethanolic extract (250 and 500 mg/kg/day) or glibenclamide (600 μg/kg/day) was administered to streptozotocin-induced male diabetic rats for 28 consecutive days. At the end of treatment, liver was harvested and activity levels of various liver enzymes were determined. Levels of thiobarbituric acid reactive substances (TBARS) were measured in liver homogenates and liver histopathological changes were observed. Results. V. vinifera seed ethanolic extract was able to prevent the decrease in ICDH, SDH, MDH, and G-6-PDH and the increase in LDH activity levels in liver homogenates. The seed extract also caused serum levels of ALT, AST, ALP, ACP, GGT, and total bilirubin to decrease while causing total proteins to increase. Additionally, the levels of ALT, AST, and TBARS in liver homogenates were decreased. Histopathological changes in the liver were reduced. Conclusion. Near normal activity levels of various enzymes and histology of the liver following V. vinifera seed ethanolic extract administration may be due to decrease in liver oxidative stress in diabetes.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  13. Rajavel V, Abdul Sattar MZ, Abdulla MA, Kassim NM, Abdullah NA
    PMID: 23243433 DOI: 10.1155/2012/195367
    Oil palm (Elaeis guineensis) leaves extract (OPLE) has antioxidant properties and because oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN), we tested the hypothesis that OPLE prevents diabetes renal oxidative stress, attenuating injury. Sprague-Dawley rats received OPLE (200 and 500 mg kg(-1)) for 4 and 12 weeks after diabetes induction (streptozotocin 60 mg kg(-1)). Blood glucose level, body and kidney weights, urine flow rate (UFR), glomerular filtration rate (GFR), and proteinuria were assessed. Oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione (GSH), and lipid peroxides (LPO) were quantified. Renal morphology was analysed, and plasma transforming growth factor-beta1 (TGF-β1) was measured. Diabetic rats demonstrated increase in blood glucose and decreased body and increased kidney weights. Renal dysfunction (proteinuria, elevations in UFR and GFR) was observed in association with increases in LPO, 8-OHdG, and TGF-β1 and a decrease in GSH. Histological evaluation of diabetic kidney demonstrated glomerulosclerosis and tubulointerstitial fibrosis. OPLE attenuated renal dysfunction, improved oxidative stress markers, and reduced renal pathology in diabetic animals. These results suggest OPLE improves renal dysfunction and pathology in diabetes by reducing oxidative stress; furthermore, the protective effect of OPLE against renal damage in diabetes depends on the dose of OPLE as well as progression of DN.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  14. Lin TS, Abd Latiff A, Abd Hamid NA, Wan Ngah WZ, Mazlan M
    PMID: 23097676 DOI: 10.1155/2012/491027
    Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream (n = 6), (II) diabetic rats receiving 0.06% tocopherol cream (n = 6), and (III) diabetic rats receiving 0.29% tocopherol cream (n = 6). Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly (P < 0.05) compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  15. Lau PS, Bidin N, Krishnan G, Nassir Z, Bahktiar H
    J Cosmet Laser Ther, 2015 Apr;17(2):86-9.
    PMID: 25260140 DOI: 10.3109/14764172.2014.968587
    Low-energy laser irradiance at certain wavelengths is able to stimulate the tissue bio-reaction and enhance the healing process. Collagen deposition is one of the important aspects in healing process because it can increase the strength of the skin. This study was designed to examine the biophotonic effect of irradiance on collagen production of diabetic wound in rat model. The tensile strength of skin was employed as a parameter to describe the wound. Diabetic rat models were induced by streptozotocin via intravenous injection. Skin-breaking strength was measured using an Instron tensile test machine. The experimental animals were treated with 808-nm diode laser at two different powers-0.1 and 0.5 W/cm(2)-and 30, 60, and 120 s for each session. The tensile strength was optimized after treated with high-power diode laser. The photostimulation effect was revealed by accelerated healing process and enhanced tensile strength of wound. Laser photostimulation on tensile strength in diabetic wound suggests that such therapy facilitates collagen production in diabetic wound healing.
    Matched MeSH terms: Diabetes Mellitus, Experimental/radiotherapy*
  16. Hani H, Allaudin ZN, Mohd-Lila MA, Ibrahim TA, Othman AM
    Xenotransplantation, 2014 Mar-Apr;21(2):174-82.
    PMID: 24645790 DOI: 10.1111/xen.12087
    BACKGROUND: Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.
    METHODS: Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.
    RESULTS: The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mM glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mM) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.
    CONCLUSIONS: Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
    KEYWORDS: caprine islets; streptozotocin‐injected mice; type 1 diabetes; xenotransplantation
    Matched MeSH terms: Diabetes Mellitus, Experimental/surgery*
  17. Ilyanie Y, Wong TW, Choo CY
    PMID: 22754938 DOI: 10.2202/1553-3840.1469
    Ficus deltoidea Jack (Moraceae) leaf extract is used as an antidiabetic in traditional medicine. Its widespread usage is reflected by the available preparations in the present commercial market. The efficacy of other Ficus species has not been entirely satisfactory and many antidiabetic herbs have demonstrated poor safety profiles. This study examined hypoglycemic and toxicity profiles of F. deltoidea leaf extract in rodent models. Extracts of dried powdered leaves were obtained using methanol solution, n-hexane, chloroform, and n-butanol. These extracts were orally administered to rodents. Their blood glucose and insulin levels, acute and subchronic toxicity, biochemical and histological profiles of liver and kidney were determined. Methanol extract exhibited blood glucose lowering activity in mildly insulin resistant diabetic rats as well as in normoglycemic mice unlike hydrophilic butanol subextract which only expressed its activity in normoglycemic mice. Methanol extract could contain both insulin receptor sensitization and secretagogue constituents. Different from toxic chloroform and hexane subextracts, hydrophilic methanol extract gave zero percent mortality up to 6400 mg/kg in 14 days. It did not induce liver and kidney toxicity upon four-week consumption at 200 mg/kg. The methanol extract possessed mixed antidiabetic actions and exhibited a low level of oral toxicity.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy*
  18. Nna VU, Bakar ABA, Ahmad A, Umar UZ, Suleiman JB, Zakaria Z, et al.
    Andrology, 2020 05;8(3):731-746.
    PMID: 31816190 DOI: 10.1111/andr.12739
    BACKGROUND: Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state.

    OBJECTIVES: The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated.

    MATERIALS AND METHODS: Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic + Malaysian propolis (300 mg/k.g. b.w.), diabetic + metformin (300 mg/kg b.w.) and diabetic + Malaysian propolis + metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.) and treatment lasted for 4 weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats.

    RESULTS: Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions.

    CONCLUSION: Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.

    Matched MeSH terms: Diabetes Mellitus, Experimental/complications*
  19. Khalil ASM, Giribabu N, Yelumalai S, Shahzad H, Kilari EK, Salleh N
    Life Sci, 2021 Aug 01;278:119605.
    PMID: 33989665 DOI: 10.1016/j.lfs.2021.119605
    Diabetes mellitus (DM) may lead to testicular-related infertility while Myristic acid (MA) is beneficial to lower hyperglycaemia. Thus, we hypothesized that MA could protect testes against hyperglycaemia-induced damage in DM. DM was induced in adult male rats by high-fat diet consumption for 12 weeks, accompanied by a single dose streptozotocin injection. Following DM confirmation, the rats were fed orally with 10 and 20 mg/kg body weight MA for 28 consecutive days. After completion of treatment, rats were sacrificed and blood, cauda epididymis and testes were harvested. Serum was separated, epididymal sperm was collected for analysis. Molecular studies of the testes were performed by qPCR, Western blotting and immunostaining. MA was found to protect the testes against oxidative stress via preventing the upregulation of RAGE, Keap1, and the downregulation of Nrf2, NQO1, HO1, SOD, CAT and GPx. MA also prevented increase in testicular inflammation and apoptosis, as indicated by low inflammatory (NF-κB p65, IKKβ, TNF-α, IL-1β and iNOS) and apoptosis (Bax and caspase-9), but high anti-apoptosis (Bcl-2) markers' levels. Besides, MA prevented the downregulation of testicular steroidogenic markers (3βHSD, 17βHSD, StAR, ARA-54 and CYP11A1). Sperm analysis revealed near normal sperm count, motility, viability, lower abnormal sperm morphology in diabetic rats received MA. MA also prevented the loss of germ cells via preventing the decreased in cell proliferative marker (PCNA) while maintaining near normal epithelial height, tubular and Leydig cell diameters in the testes in DM. MA protects the testes against damage in DM, thus maintaining spermatogenesis and steroidogenesis, consequently preserving male fertility in diabetes.
    Matched MeSH terms: Diabetes Mellitus, Experimental/complications*
  20. Giribabu N, Roslan J, Rekha SS, Salleh N
    Int J Cardiol, 2016 Nov 01;222:850-65.
    PMID: 27522389 DOI: 10.1016/j.ijcard.2016.07.250
    BACKGROUND: We hypothesized that consumption of Vitis vinifera seed by diabetics could help to ameliorate myocardial damage. Therefore, in this study, we investigated effects of V. vinifera seed methanolic extract (VVSME) on parameters related to myocardial damage in diabetes with or without myocardial infarction (MI).

    METHODS: Streptozotocin-nicotinamide induced diabetic rats received oral VVSME for 28days. MI was induced by intraperitoneal injection of isoproterenol on last two days. Prior to sacrifice, blood was collected and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid profile and insulin levels were measured. Levels of serum cardiac injury marker (troponin-I and CK-MB) were determined and histopathological changes in the heart were observed following harvesting. Levels of oxidative stress (LPO, SOD, CAT, GPx and RAGE), inflammation (NF-κB, TNF-α, IL-1β and IL-6) and cardiac ATPases (Na(+)/K(+)-ATPase and Ca(2+)-ATPase) were determined in heart homogenates. LC-MS was used to identify constituents in the extracts.

    RESULTS: Consumption of VVSME by diabetic rats with or without MI improved the metabolic profiles while decreased the cardiac injury marker levels with lesser myocardial damage observed. Additionally, VVSME consumption reduced the levels of LPO, RAGE, TNF-α, Iκκβ, NF-κβ, IL-1β and IL-6 while increased the levels of SOD, CAT, GPx, Na(+)/K(+)-ATPase and Ca(2+)-ATPase in the infarcted and non-infarcted heart of diabetic rats (p<0.05). LC-MS analysis revealed 17 major compounds in VVSME which might be responsible for the observed effects.

    CONCLUSIONS: Consumption of VVSME by diabetics helps to ameliorate damage to the infarcted and non-infarcted myocardium by decreasing oxidative stress, inflammation and cardiac ATPases dysfunctions.

    Matched MeSH terms: Diabetes Mellitus, Experimental*
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