Magnolol protects pancreatic β-cells against methylglyoxal-induced cellular dysfunction

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Chronic hyperglycemia aggravates insulin resistance, in part due to increased formation of advanced glycation end-products (AGEs). Methylglyoxal (MG), a major precursor of AGEs, accumulates abnormally in various tissues and organs and participates in oxidative damage. We investigated the insulinotropic benefits of magnolol, a hydroxylated biphenyl compound isolated from <I>Magnolia officinalis</I>, in pancreatic β-cells exposed to MG <I>in vitro</I>. When exposed to cytotoxic levels of MG for 48 h, RIN-m5F β-cells exhibited a significant loss of viability and impaired insulin secretion, whereas pretreatment with magnolol protected against MG-induced cell death and decreased insulin secretion. Moreover, magnolol increased the expression of genes involved in β-cell survival and function, including Ins2 and PDX1. Furthermore, magnolol increased the levels of AMPK phosphorylation, SIRT1, and PGC1α in RIN-5F β-cells. In addition, magnolol increased the activity of glyoxalase I and decreased the levels of MG-modified protein adducts, which suggests that magnolol protects against MG-induced protein glycation. Taken together, the results indicate the potential application of magnolol as an intervention against MG-induced hyperglycemia.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Magnolol protected against MG-induced cell death and decreased insulin secretion in RIN-5F β-cells. </LI> <LI> Magnolol increased the expression of Ins2 and PDX1 genes. </LI> <LI> Magnolol increased the levels of AMPK phosphorylation, SIRT1, and PGC1α. </LI> <LI> Magnolol increased glyoxalase 1 activity and decreased MG-modified protein adducts levels. </LI> </UL> </P>