ORCID Profile
0000-0002-8693-5506
Current Organisation
Hashemite University
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Publisher: MDPI AG
Date: 09-01-2023
Abstract: 2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p 0.001, 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p 0.001, 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p 0.001), and increased GSH level (p 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.
Publisher: Frontiers Media SA
Date: 15-07-2021
DOI: 10.3389/FPHAR.2021.695418
Abstract: The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma s les from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p & 0.01, Lysine, p & 0.001, Phenylalanine, p & 0.01, Tryptophan, p & 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D ( p & 0.01, p & 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls ( p & 0.001, p & 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls ( p & 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls ( p & 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c ( p & 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment ( p & 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications.
Publisher: Cold Spring Harbor Laboratory
Date: 26-02-2021
DOI: 10.1101/2021.02.24.21252345
Abstract: The disturbances in plasma free amino acid metabolome in diabetes mellitus was studied before but not in Jordanian population. This study aimed to assess the association between type 2 diabetes (T2D) and amino acid metabolome in a representative group of people from Jordan. Blood s les from 124 people with T2D and 67 age-, gender- and BMI-matched healthy controls were collected and assayed for glucose and HbA1c. Twenty one amino acids belonging to different categories (essential, non-essential, semi-essential, and metabolic indicators) were evaluated in both groups using amino acids analyser. Plasma free amino acids concentrations of total amino acids, total essential amino acids, total non-essential amino acids, and total semi-essential amino acids were not different in T2D compared to healthy controls. However, plasma concentrations of four essential amino acids (Leucine, Lysine, Phenylalanine, Tryptophan) were increased in the presence of T2D (Leucine, p .01, Lysine, p .001, Phenylalanine, p .01, Tryptophan, p .05). Conversely, amongst the non-essential amino acids, Alanine and Serine were reduced in type 2 diabetes (Alanine, p .01, Serine, p .001), whereas, Aspartate and Glutamate were increased in T2D compared to healthy control plasma (Aspartate, p .001, Glutamate, p .01). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p .01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2Dcompared to healthy controls (p .01). Several amino acids from different categories are dysregulated in T2D, which could be used as a therapeutic target to improve T2D management and its complications.
Publisher: Springer Science and Business Media LLC
Date: 27-10-2022
DOI: 10.1007/S11010-022-04591-1
Abstract: Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates erse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins' pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis.
Publisher: MDPI AG
Date: 04-01-2023
DOI: 10.3390/MOLECULES28020502
Abstract: Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p 0.001), increased GSH levels (p 0.001), and reduced GSSG levels (p 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for mohammed Wedyan.