Candesartan shows potential for preserving insulin secretion
MedWire News: Japanese research has revealed that candesartan may act against pancreatic β-cell lipotoxicity, suggesting it could have potential in preserving insulin secretion in patients with Type 2 diabetes.
The angiotensin receptor blocker (ARB) suppressed fatty acid-induced oxidative stress and the activation of nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in pancreatic β mouse cells, the researchers report in the journal Diabetes Research and Clinical Practice.
They say: "Our observation paved the way to possible use as a means of protecting β-cell survival and preserving capacity of insulin secretion in patients with diabetes mellitus."
An intrinsic renin-angiotensin system was recently identified in pancreatic islets, note Masanari Mizuta and colleagues at the University of Miyazaki.
As angiotensin II activates NAD(P)H oxidase, they speculated that increased activity of the renin-angiotensin system in β cells might aggravate oxidative stress-induced dysfunction in these cells and apoptosis.
The team studied whether candesartan could exert a direct effect against fatty acid-induced oxidative stress in the mouse insulin-secreting clonal cell pancreatic β-cell line MIN6 and isolated mouse pancreatic islets.
Culturing MIN6 cells in the presence of high glucose levels significantly increased their intracellular insulin content compared with when low glucose levels were used.
Adding 10 µmol candesartan for 48 hours at high glucose levels significantly increased intracellular insulin content and also counteracted the decrease in intracellular insulin content caused by palmitate, recovering levels 1.3 fold.
Upregulation of uncoupling protein-2 messenger RNA levels induced by palmitate was also suppressed by candesartan in a dose-dependent manner.
In addition, candesartan decreased the palmitate-induced accumulation of reactive oxygen species by 23% in MIN6 cells and by 59% in mouse islets.
Furthermore, candesartan decreased the palmitate-induced activity of protein kinase C in MIN6 cells by 21% and NAD(P)H oxidase activity by 37%.
The researchers summarize: "Candesartan, an ARB, suppressed fatty acid- induced oxidative stress and the activation of NAD(P)H oxidase in pancreatic β-cells."
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By Anita Wilkinson