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.
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.