DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats

2014 ◽  
Vol 307 (5) ◽  
pp. E447-E455 ◽  
Author(s):  
Lorenzo Glorie ◽  
Geert J. Behets ◽  
Lesley Baerts ◽  
Ingrid De Meester ◽  
Patrick C. D'Haese ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Strength ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Bending Test ◽  
Control Group ◽  
Mechanical Resistance ◽  
Three Point Bending ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups ( n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.

Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

2008 ◽  
Vol 294 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Chia-Ming Hsu ◽  
Chi-Hsiao Yeh ◽  
...  
Keyword(s):  
Critical Role ◽  
Serum Levels ◽  
Blood Levels ◽  
Short Term ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Dpp Iv ◽  
Before And After ◽  
Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of zinc supplementation in testes of rats with experimentally induced diabetes

2018 ◽  
Vol 43 (10) ◽  
pp. 1010-1018 ◽  
Author(s):  
Neven M. Aziz ◽  
Maha Y. Kamel ◽  
Manar S. Mohamed ◽  
Sabreen M. Ahmed
Keyword(s):  
Connexin 43 ◽  
Concomitant Administration ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Safe Alternative ◽  
Once Daily ◽  
Factor Α ◽  
Percent Area

One of the major obstacles that males with diabetes may confront is subfertility or infertility. Thus, the present study investigated the effect of co-administration of metformin and zinc (Zn) on the testes of streptozotocin-induced diabetic rats. Male albino rats were randomly divided into 4 groups: control group; untreated diabetic group; diabetic + metformin group, in which diabetic rats were treated orally with metformin (250 mg/kg) once daily for 4 weeks; and diabetic + metformin + Zn group, in which diabetic rats were treated orally with metformin in combination with Zn (10 mg/kg) once daily for 4 weeks. Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor α. Additionally, there was a significant increase in serum levels of Zn, testosterone, and follicle-stimulating hormone, as well as testicular total antioxidant capacity and anti-apoptotic protein Bcl-2, when compared with both the diabetic and metformin-treated diabetic groups. Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups. In conclusion, the combination of Zn and metformin was an efficacious and safe alternative treatment, as it had superior antihyperglycemic efficacy and provided additional benefits over metformin alone in rats with type 2 diabetes.

scholarly journals Shortened platelet half-life in multiple myeloma

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger
Keyword(s):  
Multiple Myeloma ◽  
Half Life ◽  
Serum Levels ◽  
Statistical Correlation ◽  
Control Group ◽  
Healthy Controls ◽  
Platelet Factor ◽  
Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

scholarly journals IN VITRO ANTIOXIDANT AND IN VIVO ANTIDIABETIC ACTIVITY OF TWO POTENTIAL PROBIOTIC ENTEROCOCCUS SPP. ON ALLOXAN-INDUCED DIABETIC RATS

2021 ◽  
pp. 94-98
Author(s):  
KAMNI RAJPUT ◽  
RAMESH CHANDRA DUBEY
Keyword(s):  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Control Group ◽  
Albino Rats ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Animal Group ◽  
Enterococcus Spp

Objective: In vitro antioxidant activity, in vivo antidiabetic property and intestinal attachment by two potential probiotic bacterial strains, namely, Enterococcus faecium and Enterococcus hirae were studied using albino rats. Methods: Antioxidant the activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl radicals scavenging assay. Alloxan was administered intraperitoneally to induce diabetic conditions in experimental rats. Animals were treated with oral administration of Enterococcus spp., such as E. faecium, and E. hirae isolated from goat and sheep milk. The control animal group received normal saline for the same days. Glibenclamide drug was used as a positive control against probiotic bacterial cells. Results: However, administration of probiotic bacterial strains E. faecium and E. hirae, in albino rats significantly (p<0.05) at varying doses lowered blood glucose levels in diabetic rats as compared to the diabetic control group. Both the species of Enterococcus increased the bodyweight of experimental rats. However, E. faecium was the best antidiabetic strain having the antioxidant activities also in comparison to E. hirae. The attachment of probiotic bacterial cells E. faecium on the rat’s intestine wall against pathogens was examined. Furthermore, E. faecium showed its aggregation with pathogens by attachment of the intestines of albino rats. This showed that both the bacterial strains exhibited in vivo antidiabetic effect. Conclusion: The results of this study showed that probiotic bacteria possess antioxidant, antidiabetic activities, and attachment of intestine.

scholarly journals Effects of l-Carnitine on the Follicle-Stimulating Hormone, Luteinizing Hormone, Testosterone, and Testicular Tissue Oxidative Stress Levels in Streptozotocin-Induced Diabetic Rats

2018 ◽  
Vol 23 ◽  
pp. 2515690X1879605 ◽  
Author(s):  
Nourollah Rezaei ◽  
Tahereh Mardanshahi ◽  
Majid Malekzadeh Shafaroudi ◽  
Saeed Abedian ◽  
Hamid Mohammadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Group Vi ◽  
Group I ◽  
Stimulating Hormone

The present study was designed to investigate the antioxidant property of l-carnitine (LC) on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TH) and testis oxidative stress in streptozotocin (STZ)-induced diabetic rats. The rats were divided into the following groups: group I, control; group II, LC 100 mg/kg/d; group III, diabetic; and groups IV to VI, diabetic rats treated with 50, 100, and 200 mg/kg/d of LC, respectively. Daily injections were given intraperitoneally for 7 weeks. At the end of experimental period, after sacrificing the rats, FSH, LH, TH, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), mitochondrial function (MTT), protein carbonyl (PC), and reactive oxygen species (ROS) levels were measured. STZ caused an elevation of MDA, ROS, and PC ( P < .001) with reduction of GSH, CAT, TAC, and MTT ( P < .001) in the serum levels. Group VI had significantly increased FSH, LH, and TH levels versus the untreated diabetic group ( P < .001). Although groups V and VI significantly decreased MDA ( P < .001), PC ( P < .01), and ROS ( P < .01) compared with the untreated diabetic group; only in group VI, the activity of GSH ( P < .001), CAT ( P < .01), TAC ( P < .001), and MTT ( P < .001) significantly increased. The results of the present study suggest that LC decreased diabetes-induced oxidative stress complications and also improved serum level of FSH, LH, and TH by reducing levels of lipid peroxidation and increasing antioxidant enzymes.

scholarly journals Clinical and Radiological Evaluation of Marginal Bone Loss around Dental Implants Restored with Zirconium vis-à-vis Porcelain Fused to Metal: An In Vivo Study

2020 ◽  
Vol 08 (01) ◽  
pp. 17-21
Author(s):  
Udey Singh Wirring ◽  
Tarun Kalra ◽  
Manjit Kumar ◽  
Ajay Bansal ◽  
Aquib Javaid
Keyword(s):  
Bone Loss ◽  
Dental Implants ◽  
Test Group ◽  
Radiographic Evaluation ◽  
Control Group ◽  
Marginal Bone Loss ◽  
Zirconia Crowns ◽  
Bone Level ◽  
The Difference

Abstract Introduction Marginal bone level is the criterion for implant success. Patient expectations for more natural looking implant restorations created the need to restore implants with more esthetically pleasing materials like Zirconia rather than conventional porcelain-fused to-metal (PFM) crowns. The aim of this study was to evaluate marginal bone loss around dental implants clinically and radiographically when restored with Zirconia and PFM prosthesis. Materials and Methods Two groups (control and test) were formed with 14 patients each. In the control group, the subjects were rehabilitated with PFM crowns and in the test group, the subjects were rehabilitated with Zirconia crowns. Rehabilitation was done after the healing period of 3 months. Radiographic evaluation was done at regular (baseline, 3rd, 6th, and 12th month) intervals. Results The results were statistically analyzed. Keeping in mind the limitations of the study, it was revealed that the difference in the crestal bone resorption in both the groups was not significant.

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

scholarly journals ANTIOSTEOPOROTIC ACTIVITY OF ANTHRAQUINONE ISOLATED FROM MORINDA CITRIFOLIA FRUITS IN RATS

2016 ◽  
Vol 9 (5) ◽  
pp. 209 ◽  
Author(s):  
Abin Joy ◽  
Chaitra N ◽  
Ashok M ◽  
Handral M
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Strength ◽  
Bone Mineral ◽  
Morinda Citrifolia ◽  
Bending Test ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Femur Bone ◽  
Group I

ABSTRACTObjectives: This study was designed to investigate the antiosteoporotic activity of isolated anthraquinones from Morinda citrifolia fruit extract inovariectomy (OVX) induced osteoporotic rats.Methods: All the rats were divided into 4 groups (n=6 each). Group I (sham control) received vehicle, p.o., Group II OVX control (vehicle, p.o.),Group III was OVX+standard raloxifene (5.4 mg/kg, p.o.), and Group IV was OVX+Physcion (100 mg/kg, p.o.) for 90 days.Results: The daily oral administration of isolated compound physcion (100 mg/kg) for 12 weeks to the rats prevented OVX-induced osteoporosis.This was examined by serum biomarkers such as alkaline phosphatase, calcium, and tartrate resistant acid phosphatase and showed significanteffects (p<0.0001). The femur bone strength assessed by three-point bending test showed improved bone strength in physcion treated rats, andthis was supported by enhanced bone mineral density (p<0.05). The ash parameters of femur bone studied from physcion treated rats exhibited asignificant (p<0.0001) value of ash weight followed by ash calcium content. Further, femur bone histological examination revealed the protectiveeffect of the compound physcion (100 mg/kg) against OVX-induced bone loss in rats, where it showed mineralization of trabecular spaces, improvedbone compactness thereby intact bone architecture.Conclusion: This study concludes that the isolated anthraquinone physcion had a preventive effect against OVX-induced bone loss in rats.Keywords: Morinda citrifolia, Physcion, Osteoporosis, Bone mineral density, Ash mineral content.

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

2019 ◽  
Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Pde5 Inhibitor ◽  
Corpus Cavernosum ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Intracavernosal Injection ◽  
Relaxation Responses

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.

scholarly journals α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of Euphorbia nivulia–Ham. in STZ-Induced Diabetic Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093942
Author(s):  
Muhammad Younus ◽  
Muhammad Mohtasheem ul Hasan ◽  
Khalil Ahmad ◽  
Ali Sharif ◽  
Hafiz Muhammad Asif ◽  
...  
Keyword(s):  
High Performance ◽  
Wistar Rat ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Control Group ◽  
Control Drug ◽  
Antidiabetic Effects

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.

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