Abstract
Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of Prunus persica (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of P. persica (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic β-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence β-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.
Highlights
We focused on methyl caffeate, which showed similar effects to an antidiabetic sulfonylurea drug and evaluated how it affects protein expression, including that of peroxisome proliferator-activated receptor-γ (PPARγ), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1)
In agreement with the positive effects of overexpressed PDX-1 on glucose-stimulated insulin secretion (GSIS) by treatment with resveratrol, a polyphenolic compound [54], the present study found that the protein expression of PDX-1 increased after treatment with methyl caffeate (6) in the same pattern as the protein expression of IRS-2, PI3K, and Akt
Our results showed that PRPE and caffeic acid (5), methyl caffeate (6), ferulic acid
Summary
T2DM is a result of pancreatic islet β-cell dysfunction and insulin resistance, which can lead to a deficiency in insulin secretion in response to glucose [2]. Pancreatic islet β-cells are characterized by basal secretion when unstimulated, in conditions of low glucose concentration, and in increased secretion when stimulated by high glucose concentration. These cells play an important role in blood glucose control by secreting insulin and accepting insulin regulation [3]. Identifying compounds that act like insulin, enhance pancreatic islet β-cell regeneration, or increase insulin secretion can help to develop strategies to prevent and treat T2DM. Natural products have gained attention as important resources as potential anti-T2DM bioactive compounds
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