Abu Saleh Md Moin1, Megan Cory2, Jennifer Choi2, Allison Ong2, Sangeeta Dhawan1, Sarah M Dry3, Peter C Butler2, Robert A Rizza4, Alexandra E Butler5. 1. Diabetes and Metabolism Research Institute, City of Hope, Duarte, California. 2. Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California. 4. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota. 5. Anti Doping Laboratory Qatar, Doha, Qatar.
Abstract
Context: Chronic pancreatitis (CP) is characterized by inflammation, fibrosis, and a loss of pancreatic acinar cells, which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data have implicated chromogranin A-positive hormone-negative (CPHN) cells as potential evidence of neogenesis in humans. Objective: We sought to establish if CPHN cells were more abundant in CP in humans. Design, Setting, and Participants: We investigated the frequency and distribution of CPHN cells and the expression of the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C motif receptor 3 in pancreas of nondiabetic subjects with CP. Results: CPHN cell frequency in islets was increased sevenfold in CP [2.1% ± 0.67% vs 0.35% ± 0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P < 0.01], as were the CPHN cells found as scattered cells in the exocrine areas (17.4 ± 2.9 vs 4.2 ± 0.6, CP vs NP, P < 0.001). Polyhormonal endocrine cells were also increased in CP (2.7 ± 1.2 vs 0.1 ± 0.04, CP vs NP, % of polyhormonal cells of total endocrine cells, P < 0.01), as was expression of CXCL10 in α and β cells. Conclusion: There is increased islet endogenous expression of the inflammation marker CXCL10 in islets in the setting of nondiabetic CP and an increase in polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in CP, often in a lobular distribution, may indicate foci of attempted endocrine cell regeneration.
Context:Chronic pancreatitis (CP) is characterized by inflammation, fibrosis, and a loss of pancreatic acinar cells, which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data have implicated chromogranin A-positive hormone-negative (CPHN) cells as potential evidence of neogenesis in humans. Objective: We sought to establish if CPHN cells were more abundant in CP in humans. Design, Setting, and Participants: We investigated the frequency and distribution of CPHN cells and the expression of the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C motif receptor 3 in pancreas of nondiabetic subjects with CP. Results:CPHN cell frequency in islets was increased sevenfold in CP [2.1% ± 0.67% vs 0.35% ± 0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P < 0.01], as were the CPHN cells found as scattered cells in the exocrine areas (17.4 ± 2.9 vs 4.2 ± 0.6, CP vs NP, P < 0.001). Polyhormonal endocrine cells were also increased in CP (2.7 ± 1.2 vs 0.1 ± 0.04, CP vs NP, % of polyhormonal cells of total endocrine cells, P < 0.01), as was expression of CXCL10 in α and β cells. Conclusion: There is increased islet endogenous expression of the inflammation marker CXCL10 in islets in the setting of nondiabetic CP and an increase in polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in CP, often in a lobular distribution, may indicate foci of attempted endocrine cell regeneration.
Authors: Elke M Muntjewerff; Gina Dunkel; Mara J T Nicolasen; Sushil K Mahata; Geert van den Bogaart Journal: Front Immunol Date: 2018-10-04 Impact factor: 7.561
Authors: Qiong Wei; Liang Qi; Hao Lin; Dechen Liu; Xiangyun Zhu; Yu Dai; Richard T Waldron; Aurelia Lugea; Mark O Goodarzi; Stephen J Pandol; Ling Li Journal: Front Physiol Date: 2020-10-28 Impact factor: 4.566
Authors: Megan Cory; Abu Saleh Md Moin; Antoinette Moran; Robert A Rizza; Peter C Butler; Sangeeta Dhawan; Alexandra E Butler Journal: J Endocr Soc Date: 2018-08-13