scholarly journals Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1937
Author(s):  
Shaymaa Abdulmalek ◽  
Mayada Nasef ◽  
Doaa Awad ◽  
Mahmoud Balbaa
Keyword(s):  
Type 2 Diabetes ◽  
Zinc Oxide ◽  
Memory Function ◽  
Behavioral Impairment ◽  
Curcumin Nanoparticles ◽  
Diabetes Model ◽  
Male Wistar Rats ◽  
Oxide Nanoparticle ◽  
The Brain

Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.

scholarly journals Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaymaa Abdulmalek ◽  
Asmaa Eldala ◽  
Doaa Awad ◽  
Mahmoud Balbaa
Keyword(s):  
Type 2 Diabetes ◽  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Mapk Pathway ◽  
Akt Pathway ◽  
Oxide Nanoparticles ◽  
Curcumin Nanoparticles ◽  
Ameliorative Effect ◽  
Low Toxicity

AbstractThe present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway’s molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes

2018 ◽  
Vol 39 (5) ◽  
pp. 719-738 ◽  
Author(s):  
Megan E Capozzi ◽  
Richard D DiMarchi ◽  
Matthias H Tschöp ◽  
Brian Finan ◽  
Jonathan E Campbell
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Drug Class ◽  
Clinical Findings ◽  
Metabolic Dysfunction ◽  
Multiple Receptors ◽  
Insulinotropic Peptide ◽  
The Brain

Abstract Glucagonlike peptide 1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of glucagonlike peptide 1 receptor–directed strategies is submaximal, and the only potent, sustainable treatment of metabolic dysfunction is bariatric surgery, necessitating the development of unique therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors. In this review, we discuss the range of tissue targets and added benefits afforded by the inclusion of each of GIP and glucagon. We discuss considerations for the development of sequence-intermixed dual agonists and triagonists, highlighting the importance of evaluating balanced signaling at the targeted receptors. Several multireceptor agonist peptides have been developed and evaluated, and the key preclinical and clinical findings are reviewed in detail. The biological activity of these multireceptor agonists are founded in the success of GLP-1-directed strategies; by including GIP and glucagon components, these multireceptor agonists are thought to enhance GLP-1’s activities by broadening the tissue targets and synergizing at tissues that express multiple receptors, such at the brain and pancreatic isletβ cells. The development and utility of balanced, unimolecular multireceptor agonists provide both a useful tool for querying the actions of incretins and glucagon during metabolic disease and a unique drug class to treat type 2 diabetes with unprecedented efficacy.

scholarly journals Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sophie Bauer ◽  
Charlotte Wennberg Huldt ◽  
Kajsa P. Kanebratt ◽  
Isabell Durieux ◽  
Daniela Gunne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pancreatic Islets ◽  
Ex Vivo ◽  
Functional Coupling ◽  
Human Pancreatic Islets ◽  
Diabetes Model

scholarly journals PRM58 Long-Term Validation of the IMS CORE Diabetes Model in Type 1 and Type 2 Diabetes

2012 ◽  
Vol 15 (7) ◽  
pp. A470 ◽  
Author(s):  
V. Foos ◽  
J.L. Palmer ◽  
D. Grant ◽  
A. Lloyd ◽  
M. Lamotte ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Model

scholarly journals The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Kira V. Derkach ◽  
Vera M. Bondareva ◽  
Oxana V. Chistyakova ◽  
Lev M. Berstein ◽  
Alexander O. Shpakov
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Brain Serotonin ◽  
Serotonin Level ◽  
High Fat ◽  
Brain Serotonin Level ◽  
The Brain

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation byβ-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

scholarly journals Effect of metformin on the expression of SNAER proteins in the skeletal muscle of rats with type 2 diabetes

2021 ◽  
pp. 270-278
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Snare Complex ◽  
Snare Proteins ◽  
Glucose Levels ◽  
Male Wistar Rats

Background and Aims: SNARE proteins are composed of a combination of SNAP-23, Stx-4, and VAMP-2 isoforms that are significantly expressed in skeletal muscle. These proteins control the transport of GLUT4 to the cell membranes. The modifications in the expression of SNARE proteins can cause Type 2 diabetes. The present study aimed to assess the effect of metformin on the expression of these proteins in rats. Materials and Methods: For the purpose of the study, 40 male Wistar rats were randomly selected. Streptozotocin and Nicotinamide were used for the induction of type 2 diabetes. The animals were assigned to five groups (n=8), including healthy and diabetic groups as control, as well as three experimental groups which were treated with different doses of metformin (100, 150, and 200 mg/kg body weight) for 30 days. The quantitative reverse transcription PCR (RT-qPCR) method was applied to evaluate the expression of SNARE complex proteins.. Results: Based on the results, metformin (100, 150, and 200 mg/kg body weight) decreased serum glucose levels and increased serum insulin levels. This difference in dose of 200 mg/kg body weight was statistically significant (P<0.05). Moreover, all three doses of metformin increased the expression of SNAP- 23, syntaxin-4, and VAMP-2 proteins in skeletal muscle tissue. Metformin at a dose of 200 mg/kg body weight demonstrated the most significant effects (P<0.05). Conclusion: As evidenced by the results of the current study, another anti-diabetic mechanism of metformin is to increase the expression of SNARE proteins, which effectively improves insulin resistance and lowers blood glucose.

scholarly journals Antioxidant status and hepato-protective role of Anchomanes difformis in streptozotocin-induced diabetes in male Wistar rats

2020 ◽  
Vol 66 (1) ◽  
pp. 18-36
Author(s):  
Toyin D. Alabi ◽  
Nicole L. Brooks ◽  
Oluwafemi O. Oguntibeju
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Aqueous Extract ◽  
Liver Dysfunction ◽  
Antioxidant Status ◽  
Wistar Rats ◽  
Serum Levels ◽  
Male Wistar Rats ◽  
Hepatic Injuries

SummaryIntroduction: The liver is involved in the metabolism of xenobiotics and their metabolites and it is vulnerable to oxidative damage. Hyperglycaemia is highly implicated in the progression of diabetes mellitus, and adversely affects the liver. Though, conventional hypoglycaemic drugs may be effective in reducing blood glucose, they do not appear to be effective in attenuating the progression of diabetes and its complications.Objective: This study evaluated the ameliorative effects of Anchomanes difformis on hyperglycaemia and hepatic injuries in type 2 diabetes.Methods: Type 2 diabetes was induced in male Wistar rats with a single intraperitoneal injection of streptozotocin (40 mg/kg BW) after two weeks of fructose (10%) administration. Aqueous extract of A. difformis (200 and 400 mg/kg BW) and glibenclamide (5 mg/kg BW) were administered orally for six weeks. Blood glucose concentrations were measured. Serum levels of liver dysfunction markers (ALT, AST, and ALP), total cholesterol, triglycerides, HDL- and LDL-cholesterol were investigated. Total protein, albumin, and globulin were also assessed. Antioxidant parameters: ORAC, GSH, GSSG, SOD, CAT and FRAP were evaluated in the liver while ORAC, FRAP and lipid peroxidation were determined in the serum. Histological examination of the liver tissue was carried out.Results: Treatment with aqueous extract of A. difformis significantly (p<0.05) reduced blood glucose and reversed steatosis in the diabetic-treated rats. The antioxidant status of diabetic-treated rats was significantly (p<0.05) improved. Serum levels of liver dysfunction markers were significantly (p<0.05) reduced in diabetic-treated rats.Conclusion: The findings in this study revealed that 400 mg/kgBW Anchomanes difformis was more effective than 200 mg/kg BW in ameliorating diabetes-induced hepatopathy, however, both doses of Anchomanes difformis demonstrated more antidiabetic ability than glibenclamide. Anchomanes difformis may be a novel and potential therapeutic agent in the management of diabetes and resulted hepatic injuries.

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