Antrodia camphorata Increases Insulin Secretion and Protects from Apoptosis in MIN6 Cells.

Chi Teng Vong,Hisa Hui Ling Tseng,Simon Ming-Yuen Lee,Yiu Wa Kwan,Maggie Pui Man Hoi

doi:10.3389/fphar.2016.00067

Abstract

Antrodia camphorata is a Taiwanese-specific fungus which has been used clinically to treat hypertension, immune- and liver-related diseases and cancer; however, it has never been studied in type 2 diabetes mellitus (T2DM). Hyperglycemia in T2DM causes endoplasmic reticulum (ER) stress, leading to β-cell dysfunction. During chronic ER stress, misfolded proteins accumulate and initiate β-cell apoptosis. Moreover, β-cell dysfunction leads to defect in insulin secretion, which is the key process in the development and progression of T2DM. Therefore, the aim of the present study was to examine the effects of A. camphorata on insulin secretion and ER stress-induced apoptosis in a mouse β-cell line, MIN6, and their underlying mechanisms. We demonstrated that the ethanolic extract of A. camphorata increased glucose-induced insulin secretion dose-dependently through peroxisome proliferator-activated receptor-γ (PPAR-γ) pathway, and upregulated genes that were involved in insulin secretion, including PPAR-γ, glucose transporter-2 and glucokinase. Furthermore, A. camphorata slightly increased cell proliferation, as well as protected from ER stress-induced apoptosis in MIN6 cells. In conclusion, this study provided evidences that A. camphorata might have anti-diabetic effects and could be a novel drug for T2DM.

Highlights

Antrodia camphorata is a Taiwanese-specific fungus, which has been used as traditional medicine to treat cancer, hypertension and skin itching, and it has anti-oxidant and anti-inflammatory effects (Geethangili and Tzeng, 2011)
peroxisome proliferator-activated receptor-γ (PPAR-γ) (D69), ki-67 (D3B5) mAb, Caspase-3, β-actin, α,β-Tubulin and GAPDH antibodies, and anti-rabbit-HRP secondary antibodies were obtained from Cell Signaling Technology (USA), while GLK, p-inositol requiring 1α (IRE1α), IRE1α antibodies were obtained from Abcam (USA). p-PERK, PERK antibodies were purchased from LifeSpan BioSciences (USA), while glucose transporter-2 (GLUT-2) (H-67) and activating transcription factor 6α (ATF6α) (H-280) antibodies were purchased from Santa Cruz Biotechnology (USA)
After treatment with A. camphorata for 24 h, MIN6 cells were incubated with Krebs–Ringer bicarbonate buffer (KRBB) 5.5 mM or 16.7 mM glucose for 1 h, the supernatants were collected for insulin ELISA

Summary

Introduction

Antrodia camphorata is a Taiwanese-specific fungus, which has been used as traditional medicine to treat cancer, hypertension and skin itching, and it has anti-oxidant and anti-inflammatory effects (Geethangili and Tzeng, 2011). PPAR-γ belongs to the nuclear receptor superfamily which is expressed in β-cells, and it forms heterodimers with RXR in order to bind to the PPRE on gene promoters and activates gene transcription (Kim and Ahn, 2004). It has been reported the presence of PPRE in the GLUT-2 and GLK promoters, which are involved in insulin secretion (Kim et al, 2000, 2002). The effect of A. camphorata in insulin secretion has not been studied in pancreatic β-cells

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