Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2018; 24(28): 3120-3129
Published online Jul 28, 2018. doi: 10.3748/wjg.v24.i28.3120
Impact of hyperglycemia on autoimmune pancreatitis and regulatory T-cells
Franz-Tassilo Müller-Graff, Brit Fitzner, Robert Jaster, Brigitte Vollmar, Dietmar Zechner
Franz-Tassilo Müller-Graff, Brigitte Vollmar, Dietmar Zechner, Institute for Experimental Surgery, Rostock University Medical Center, Rostock 18057, Germany
Brit Fitzner, Robert Jaster, Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock 18057, Germany
Author contributions: FTMG and BF performed experiments; RJ evaluated histological sections; DZ designed and performed experiments; FTMG and DZ wrote the manuscript; all authors interpreted the results and revised the manuscript.
Supported by the Deutsche Forschungsgemeinschaft (DFG research group FOR 2591), No. 321137804, No. ZE 712/1-1 and No. VO 450/15-1.
Institutional animal care and use committee statement: All experiments were executed in accordance with the German legislation, the EU-directive 2010/63/EU and approved by the Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei Mecklenburg-Vorpommern (7221.3-1.1-004/13).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Data are available from the corresponding author at
ARRIVE guidelines statement: The Manuscript was prepared and revised according to the ARRIVE guidelines.
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:
Correspondence to: Dietmar Zechner, PhD, Academic Research, Senior Scientist, Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, Rostock 18057, Germany.
Telephone: +49-381-4942512 Fax: +49-381-4942502
Received: April 17, 2018
Peer-review started: April 17, 2018
First decision: June 11, 2018
Revised: June 17, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: July 28, 2018

To evaluate the influence of hyperglycemia on the progression of autoimmune pancreatitis.


We induced hyperglycemia by repetitive intraperitoneal (ip) injection of 50 mg/kg streptozotocin in MRL/MpJ mice, which develop autoimmune pancreatitis due to a genetic predisposition. We compared the extent of inflammation (histological score, CD3+ lymphocytes, CD8+ T-cells, CD4+ T-cells, Foxp3+ T-helper cells) in the pancreas of hyperglycemic and normoglycemic mice. We also analyzed the number of leukocytes, lymphocytes, granulocytes and monocytes in the blood. In addition, we determined the percentage of CD3+ lymphocytes, CD8+ T-cells, CD4+ T-cells, Foxp3+ T-helper cells, Foxp3+ CD25+ T-helper and Foxp3- T-helper cells in the spleen by flow cytometry.


Treatment with streptozotocin caused a strong induction of hyperglycemia and a reduction in body weight (P < 0.001). Severe hyperglycemia did not, however, lead to an aggravation, but rather to a slight attenuation of autoimmune pancreatitis. In the pancreas, both the histological score of the pancreas as well as the number of CD3+ lymphocytes (P < 0.053) were decreased by hyperglycemia. No major changes in the percentage of CD8+ T-cells, CD4+ T-cells, Foxp3+ T-helper cells were observed between hyperglycemic and normoglycemic mice. Hyperglycemia increased the numbers of leukocytes (P < 0.001), lymphocytes (P = 0.016), granulocytes and monocytes (P = 0.001) in the blood. Hyperglycemia also moderately reduced the percentage of CD3+ lymphocytes (P = 0.057), significantly increased the percentage of Foxp3+ T-helper cells (P = 0.018) and Foxp3+ CD25+ T-helper cells (P = 0.021) and reduced the percentage of Foxp3- T-helper cells (P = 0.034) in the spleen.


Hyperglycemia does not aggravate but moderately attenuates autoimmune pancreatitis, possibly by increasing the percentage of regulatory T-cells in the spleen.

Keywords: Autoimmune disease, Diabetes, Treg, FoxP3, Autoimmune pancreatitis, MRL/MpJ mice

Core tip: Temporary or sustained hyperglycemia can be observed in about 42%-66% of patients with autoimmune pancreatitis. However, it is unknown to what extent hyperglycemia has an influence on the course of this disease. This preclinical study demonstrates that hyperglycemia does not lead to an aggravation but rather an attenuation of autoimmune pancreatitis. Thus, this result might have the clinical implication that a tight adjustment of blood glucose concentration in patients with autoimmune pancreatitis is not needed, because it might not have a beneficial effect on the progression of this disease.