{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:14:45Z","timestamp":1791065685126,"version":"4.1.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"6","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,6,1]]},"abstract":"<jats:p>The relationship between oxidation stress and phosphoinositide 3-kinase (PI3K) signaling in pancreatic \u03b2-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 \u03b2-cell\u2013derived 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\u2013related, 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\u2013induced oxidative stress and PI3K activation cause Akt signaling\u2013related pancreatic \u03b2-cell dysfunction.<\/jats:p>","DOI":"10.2337\/db06-0029","type":"journal-article","created":{"date-parts":[[2006,5,26]],"date-time":"2006-05-26T20:00:23Z","timestamp":1148673623000},"page":"1614-1624","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":114,"title":["The Role of Phosphoinositide 3-Kinase\/Akt Signaling in Low-Dose Mercury\u2013Induced Mouse Pancreatic \u03b2-Cell Dysfunction In Vitro and In Vivo"],"prefix":"10.2337","volume":"55","author":[{"given":"Ya Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Fa","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keh Sung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Chieh","family":"Yen","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Occupational Safety and Health, College of Health Care and Management, Chung San Medical University, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Yao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Traumatology, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Surgery, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoei Yn","family":"Lin-Shiau","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Surgery, National Taiwan University, Taipei, Taiwan"},{"name":"Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031210155714100_R1","doi-asserted-by":"crossref","unstructured":"Finkel T, Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. 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