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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2015; 6(4): 131-139
Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.131
Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature
Run Yu, Yun Zheng, Matthew B Lucas, Yun-Guang Tong
Run Yu, Carcinoid and Neuroendocrine Tumor Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Yun Zheng, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China
Matthew B Lucas, Princeton University, Princeton, NJ 08544, United States
Yun-Guang Tong, Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, United States
Yun-Guang Tong, Department of Pathology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Author contributions: All authors contributed to this paper.
Supported by National Cancer Institute of the National Institutes of Health, No. R00CA138914 (YT); and by National Natural Science Foundation, No. 81372216 (YT).
Conflict-of-interest statement: The authors have no conflicts of interest to disclose. Dr. Yunguang Tong is supported by the National Cancer Institute of the National Institutes of Health under award number R00CA138914 (YT) and National Natural Science Foundation under grant number 81372216 (YT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Run Yu, MD, PhD, Carcinoid and Neuroendocrine Tumor Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd, B-131, Los Angeles, CA 90048, United States. run.yu@cshs.org
Telephone: +1-310-4234774 Fax: +1-310-4230440
Received: April 1, 2015
Peer-review started: April 2, 2015
First decision: June 18, 2015
Revised: July 3, 2015
Accepted: July 24, 2015
Article in press: July 27, 2015
Published online: November 15, 2015
Abstract

Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions so that understanding the physiological, cellular, and molecular mechanisms underlying the pathogenesis of precursor lesions is critical for the prevention and treatment of those neoplasms. Pancreatic neuroendocrine tumors (PNETs) can also be derived from precursor lesions. Pancreatic α cell hyperplasia (ACH), a specific and overwhelming increase in the number of α cells, is a precursor lesion leading to PNET pathogenesis. One of the 3 subtypes of ACH, reactive ACH is caused by glucagon signaling disruption and invariably evolves into PNETs. In this article, the existing work on the mechanisms underlying reactive ACH pathogenesis is reviewed. It is clear that the liver secretes a humoral factor regulating α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.

Keywords: Pancreatic α cell hyperplasia, Humoral factor, Pancreatic neuroendocrine tumors, Digestive system hormone, Liver

Core tip: Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions. One of the precursor lesions, reactive pancreatic α cell hyperplasia is caused by glucagon signaling disruption and invariably evolves into pancreatic neuroendocrine tumors. In this article, the existing work on the mechanisms underlying the novel precursor lesion is reviewed. It is clear that the liver secretes a humoral factor regulating pancreatic α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.