Alterations in Pancreatic Protein Expression in STZ-Induced Diabetic Rats and Genetically Diabetic Mice in Response to Treatment with Hypoglycemic Dipeptide Cyclo (His-Pro)

Ang-1 (angiopoietin-1) improves the ineffective angiogenesis and impaired wound healing in diabetes; however, the mechanism underlying this positive effect is still far from being completely understood. In the present study, we investigated whether rAAV (recombinant adeno-associated virus)–Ang-1 gene transfer could improve wound repair in genetically diabetic mice (db+/db+) and the mechanism(s) by which it causes new vessel formation. An incisional skin-wound model in diabetic and normoglycaemic mice was used. After the incision, animals received rAAV–LacZ or rAAV–Ang-1 in the wound edge. After 7 and 14 days, wounds were used to (i) confirm Ang-1 gene transfer, (ii) assess histologically the healing process, (iii) evaluate wound-breaking strength, and (iv) study new vessel formation by PECAM-1 (platelet/endothelial cell adhesion molecule-1) immunostaining. Finally, we investigated VEGF (vascular endothelial growth factor) mRNA and protein levels, eNOS (endothelial NO synthase) expression and VEGFR-1 and VEGFR-2 (VEGF receptor-1 and -2 respectively) immunostaining. The efficiency of Ang-1 gene transfer was confirmed by increased mRNA and protein expression of the protein. rAAV–Ang-1 significantly improved the healing process, stimulating re-epithelization and collagen maturation, increasing breaking strength and significantly augmenting the number of new vessels, as indicated by PECAM-1 immunostaining. However, Ang-1 gene transfer did not modify the decrease in VEGF mRNA and protein expression in diabetic mice; in contrast, Ang-1 increased eNOS expression and augmented nitrate wound content and VEGFR-2 immunostaining and protein expression. Ang-1 gene transfer did not change vascular permeability. Similar results were obtained in normoglycaemic animals. In conclusion, our results provide strong evidence that Ang-1 gene transfer improves the delayed wound repair in diabetes by inducing angiogenesis in a VEGF-independent manner.

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Anti-Diabetic Activity of a Mineraloid Isolate, in vitro and in Genetically Diabetic Mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000048 ◽

2011 ◽

Vol 81 (1) ◽

pp. 34-42 ◽

Cited By ~ 1

Author(s):

Joel Deneau ◽

Taufeeq Ahmed ◽

Roger Blotsky ◽

Krzysztof Bojanowski

Keyword(s):

Dna Microarrays ◽

Human Fibroblasts ◽

Diabetic Animal ◽

In Vitro Tests ◽

Diabetic Mice ◽

Fossil Material ◽

Expression Of Genes ◽

Enhanced Expression ◽

Genetically Diabetic Mice

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

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P1191 Recombinant adeno-associated virus vector-mediated human VEGF165 gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mice

European Heart Journal ◽

10.1016/s0195-668x(03)94483-6 ◽

2003 ◽

Vol 24 (5) ◽

pp. 222

Author(s):

B DEODATO

Keyword(s):

Wound Healing ◽

Gene Transfer ◽

Virus Vector ◽

Diabetic Mice ◽

Adeno Associated Virus ◽

Genetically Diabetic Mice

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Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice

Diabetes ◽

10.2337/diabetes.34.11.1075 ◽

1985 ◽

Vol 34 (11) ◽

pp. 1075-1081 ◽

Cited By ~ 1

Author(s):

T. H. Kuo ◽

F. Giacomelli ◽

J. Wiener ◽

K. Lapanowski-Netzel

Keyword(s):

Dehydrogenase Activity ◽

Pyruvate Dehydrogenase ◽

Diabetic Mice ◽

Cardiac Mitochondria ◽

Genetically Diabetic Mice

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Defective oxidative metabolism of heart mitochondria from genetically diabetic mice

Diabetes ◽

10.2337/diabetes.32.9.781 ◽

1983 ◽

Vol 32 (9) ◽

pp. 781-787 ◽

Cited By ~ 13

Author(s):

T. H. Kuo ◽

K. H. Moore ◽

F. Giacomelli ◽

J. Wiener

Keyword(s):

Oxidative Metabolism ◽

Heart Mitochondria ◽

Diabetic Mice ◽

Genetically Diabetic Mice

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Neuropeptide Y increases food intake in mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.253.3.r516 ◽

1987 ◽

Vol 253 (3) ◽

pp. R516-R522 ◽

Cited By ~ 8

Author(s):

J. E. Morley ◽

E. N. Hernandez ◽

J. F. Flood

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Water Intake ◽

Free Acid ◽

Behavioral Analysis ◽

Intracerebroventricular Administration ◽

Diabetic Mice ◽

Number Of Species ◽

Genetically Diabetic Mice ◽

Old Mice

Neuropeptide Y (NPY) stimulates eating in a number of species. In the studies reported here, intracerebroventricular administration of porcine NPY increased eating in mice. In the presence of food, NPY caused enhancement of water intake, whereas in the absence of food, NPY suppressed water intake. Behavioral analysis showed that NPY decreased the latency to eat, increased the time spent eating, and decreased grooming. Human NPY also increased food intake, whereas the free acid of NPY was inactive. Although some minor discrepancies in response were noted overall, NPY was as effective at stimulating food intake in genetically obese (ob/ob) mice compared with their lean littermates (ob/-), in genetically diabetic mice (db/db) and their nondiabetic heterozygote control (db/m), in streptozocin-induced diabetic mice and their controls, and in adult (8 mo old) compared with old (25 mo old) mice.

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PO-086 Exercise enhances cardiac antioxidant capacity in diabetic rats through the Keap1/Nrf2 signaling pathway

Exercise Biochemistry Review ◽

10.14428/ebr.v1i3.11603 ◽

2018 ◽

Vol 1 (3) ◽

Author(s):

Shiqiang Wang

Keyword(s):

Oxidative Stress ◽

Blood Glucose ◽

Protein Expression ◽

Signaling Pathway ◽

Diabetic Rats ◽

Heart Weight ◽

Stress Injury ◽

Myocardial Oxidative Stress ◽

Nrf2 Signaling Pathway ◽

Gene And Protein Expression

Objective To investigate the effects of exercise on the myocardial oxidative stress injury of diabetic rats, and discussed the role of Keap1/Nrf2 signaling pathway in this process Methods Tyep 2 diabetic rat model was established by streptozotocin injection through abdominal cavity and high fat diet. The all the diabetic rats were divided into three groups: control group (NC), diabetes group(T2DM) and diabetes exercise group, NC and T2DM group were kept quiet for 8 weeks, T2DME group was trained for 8 weeks. After the exercise, weight, heart weight and blood were measured. MDA, T-SOD and GSH-PX enzyme were measured by biochemical method. Ho-1, Keap1, Nrf2 gene and protein expression were detected by RT-PCR and WesternBlotting. Results Compared with NC group, the weight of rats in the T2DM group significantly decreased [(528+/-71g vs 362+/-33g), P<0.05], HWI significantly increased [(2.845+/-0.22 vs 3.841+/-0.21, P <0.05], blood glucose was significantly increased [(6.4±3.8 vs 26±7.5mmol/L), P <0.01],T-SOD and GSH-PX activity decreased significantly (P<0.05), Ho-1 protein expression increased (P<0.01), Keap1 and Nrf2 showed no significant changes, and Nrf2 nuclear transposition decreased (P<0.05). Compared with the T2DM group, no significant change in body weight and heart weight in the T2DME group, with significant decrease in HWI[（3.841±0.21 vs 3.235±0.23），P＜0.05], with significant decrease in blood glucose [（26.0±7.5 vs 21.0±6.8），P＜0.05]. Ho-1 gene and protein expression increased significantly（P＜0.05and P＜0.01）, with no significant change of Keap1, while Nrf2 expression increased significantly (P < 0.05), and Nrf2 nuclear transposition increased significantly (P < 0.01). Conclusions Exercise activates the myocardial Keap1/Nrf2 signaling pathway in rats, promotes the expression of downstream antioxidant enzymes, increases cardiac antioxidant capacity, and resists diabetic myocardial oxidative stress injury.

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