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 dietmar.zechner@uni-rostock.de.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dietmar Zechner, PhD, Academic Research, Senior Scientist, Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, Rostock 18057, Germany. dietmar.zechner@uni-rostock.de
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
ARTICLE HIGHLIGHTS
Research background

In about 42%-66% of patients with autoimmune pancreatitis, hyperglycemia can be observed. Thus, hyperglycemia is a frequent and important complication of this disease. However, it is not known if it merely reflects the severity of pancreatitis or whether it can also influence the progression of autoimmune pancreatitis.

Research motivation

For treating autoimmune pancreatitis in the clinic, guidelines recommend to adjust blood glucose concentration before starting a steroid therapy. However, critical attitudes towards adjusting the blood glucose concentration in these patients have also been published. For example, in one third of all cases, hyperglycemia even worsened after insulin therapy, and treatment of diabetes with insulin sometimes leads to hypoglycemic attacks in patients. In order to decide how important a tight adjustment of blood glucose concentration in patients with autoimmune pancreatitis is, we need to know if hyperglycemia has a positive or negative influence on the progression of this disease.

Research objectives

The purpose of this present study was to address the question of whether diabetes can influence the progression of autoimmune pancreatitis and to analyze which aspects of this disease are affected by hyperglycemia.

Research methods

We chose to use MRL/MpJ mice, an animal model widely used to study autoimmune pancreatitis. These mice spontaneously develop autoimmune pancreatitis. We induced hyperglycemia by repetitive intraperitoneal (ip) injection of streptozotocin in female mice and compared the extent of inflammation in the pancreas of hyperglycemic and normoglycemic animals. We also analyzed the number of immune cells in the blood. In addition, we determined the percentage of T-cells, especially regulatory T-cells in the spleen.

Research results

Surprisingly, experimental hyperglycemia did not cause an aggravation of autoimmune pancreatitis, but moderately improved autoimmune pancreatitis. We noticed an increased percentage of regulatory T-cells in the spleen, as well as an increased number of leukocytes in the blood of hyperglycemic mice. These findings suggest that hyperglycemia might rather influence the overall immune system and only indirectly affect autoimmune pancreatitis itself.

Research conclusions

Our preclinical study on mice supports the idea that an aggressive adjustment of blood glucose concentration might not be necessary as a prerequisite for the treatment of patients with autoimmune pancreatitis.

Research perspectives

A clinical study that evaluates whether a tight adjustment of blood glucose is beneficial or harmful to patients should be pursued.