Search results for: hyperglycaemia

Authors: Hong Ding, Fatiha Benslimane, Isra Marei, Chris R. Triggle

Abstract:

Hyperglycaemia is a key factor that contributes to the development of diabetes-related microvascular disease and a major risk factor for endothelial dysfunction. In the current study, we have explored glucose-induced abnormal intracellular calcium (Ca2+ i) homeostasis in mouse microvessel endothelial cells (MMECs) in high glucose (HG) (40mmol/L) versus control (low glucose, LG) (11 mmol/L). We demonstrated that the exposure of MMECs to HG for 3 days did not change basal Ca2+ i, however, there was a significant increase of acetylcholine-induced Ca2+ entry. Western blots illustrated that exposure to HG also increased STIM1 (Stromal Interaction Molecule 1), but not Orai1 (the pore forming subunit), protein expression levels. Although the link between HG-induced changes in STIM1 expression, enhanced Ca2+ entry and endothelial dysfunction requires further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.

Keywords: store-operated calcium entry, hyperglycaemia, STIM1, endothelial dysfunction

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

Abstract:

This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMSQTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg·bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: Diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid.

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