HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. W. Articles by Liu, S. H. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. W. Articles by Liu, S. H. Social Bookmarking                What's this?

The Role of Phosphoinositide 3-Kinase/Akt Signaling in Low-Dose Mercury–Induced Mouse Pancreatic ß-Cell Dysfunction In Vitro and In Vivo

¹ Institute of Toxicology, National Taiwan University, Taipei, Taiwan
² Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan
³ Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan
⁴ Department of Occupational Safety and Health, College of Health Care and Management, Chung San Medical University, Taichung, Taiwan
⁵ Department of Traumatology, National Taiwan University, Taipei, Taiwan
⁶ Department of Surgery, National Taiwan University, Taipei, Taiwan
⁷ Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan

Address correspondence and reprint requests to Shing-Hwa Liu, PhD, Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, 10043, Taiwan. E-mail: shliu{at}ha.mc.ntu.edu.tw

Abbreviations: DCF, dichlorofluorescein; DCFH-DA, DCF diacetate; ELISA, enzyme-linked immunosorbent assay; KRB, Krebs Ringer buffer; MeHg, methylmercury; NAC, N-acetyl-L-cysteine; PI3K, phosphoinositide 3-kinase; ROS, reactive oxygen species

The relationship between oxidation stress and phosphoinositide 3-kinase (PI3K) signaling in pancreatic ß-cell dysfunction remains unclear. Mercury is a well-known toxic metal that induces oxidative stress. Submicromolar-concentration HgCl₂ or methylmercury triggered reactive oxygen species (ROS) production and decreased insulin secretion in ß-cell–derived HIT-T15 cells and isolated mouse islets. Mercury increased PI3K activity and its downstream effector Akt phosphorylation. Antioxidant N-acetyl-L-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. These results indicate that both PI3K and ROS independently regulated Akt signaling–related, mercury-induced insulin secretion inhibition. We next observed that 2- or 4-week oral exposure to low-dose mercury to mice significantly caused the decrease in plasma insulin and displayed the elevation of blood glucose and plasma lipid peroxidation and glucose intolerance. Akt phosphorylation was shown in islets isolated from mercury-exposed mice. NAC effectively antagonized mercury-induced responses. Mercury-induced in vivo effects and increased blood mercury were reversed after mercury exposure was terminated. These results demonstrate that low-dose mercury–induced oxidative stress and PI3K activation cause Akt signaling–related pancreatic ß-cell dysfunction.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. C. Chuang, R. S. Yang, K. S. Tsai, F. M. Ho, and S. H. Liu Hyperglycemia Enhances Adipogenic Induction of Lipid Accumulation: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2, Phosphoinositide 3-Kinase/Akt, and Peroxisome Proliferator-Activated Receptor {gamma} Signaling Endocrinology, September 1, 2007; 148(9): 4267 - 4275. [Abstract] [Full Text] [PDF]