Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress

doi:10.1038/nm.3705

. 2014 Dec;20(12):1417-26.

doi: 10.1038/nm.3705. Epub 2014 Nov 2.

Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress

Sumaira Z Hasnain¹, Danielle J Borg², Brooke E Harcourt², Hui Tong¹, Yonghua H Sheng¹, Choa Ping Ng³, Indrajit Das¹, Ran Wang¹, Alice C-H Chen¹, Thomas Loudovaris⁴, Thomas W Kay⁴, Helen E Thomas⁴, Jonathan P Whitehead⁵, Josephine M Forbes⁶, Johannes B Prins⁷, Michael A McGuckin⁸

Affiliations

¹ Mucosal Diseases Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
² Glycation &Diabetes Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
³ Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
⁴ St. Vincent's Research Institute, Melbourne, Victoria, Australia.
⁵ 1] Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
⁶ 1] Glycation &Diabetes Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁷ 1] Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁸ 1] Mucosal Diseases Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia. [3] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

PMID: 25362253
DOI: 10.1038/nm.3705

Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress

Sumaira Z Hasnain et al. Nat Med. 2014 Dec.

. 2014 Dec;20(12):1417-26.

doi: 10.1038/nm.3705. Epub 2014 Nov 2.

Authors

Affiliations

¹ Mucosal Diseases Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
² Glycation &Diabetes Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
³ Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
⁴ St. Vincent's Research Institute, Melbourne, Victoria, Australia.
⁵ 1] Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
⁶ 1] Glycation &Diabetes Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁷ 1] Metabolic Medicine Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁸ 1] Mucosal Diseases Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. [2] School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia. [3] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

PMID: 25362253
DOI: 10.1038/nm.3705

Abstract

In type 2 diabetes, hyperglycemia is present when an increased demand for insulin, typically due to insulin resistance, is not met as a result of progressive pancreatic beta cell dysfunction. This defect in beta cell activity is typically characterized by impaired insulin biosynthesis and secretion, usually accompanied by oxidative and endoplasmic reticulum (ER) stress. We demonstrate that multiple inflammatory cytokines elevated in diabetic pancreatic islets induce beta cell oxidative and ER stress, with interleukin-23 (IL-23), IL-24 and IL-33 being the most potent. Conversely, we show that islet-endogenous and exogenous IL-22, by regulating oxidative stress pathways, suppresses oxidative and ER stress caused by cytokines or glucolipotoxicity in mouse and human beta cells. In obese mice, antibody neutralization of IL-23 or IL-24 partially reduced beta cell ER stress and improved glucose tolerance, whereas IL-22 administration modulated oxidative stress regulatory genes in islets, suppressed ER stress and inflammation, promoted secretion of high-quality efficacious insulin and fully restored glucose homeostasis followed by restitution of insulin sensitivity. Thus, therapeutic manipulation of immune regulators of beta cell stress reverses the hyperglycemia central to diabetes pathology.

PubMed Disclaimer

Comment in

A role for interleukin-22 in the alleviation of metabolic syndrome.
Dalmas E, Donath MY. Dalmas E, et al. Nat Med. 2014 Dec;20(12):1379-81. doi: 10.1038/nm.3748. Epub 2014 Nov 2. Nat Med. 2014. PMID: 25362255

Cited by

Effect of Different Volumes of Interval Training and Continuous Exercise on Interleukin-22 in Adults with Metabolic Syndrome: A Randomized Trial.
Ramos JS, Dalleck LC, Stennett RC, Mielke GI, Keating SE, Murray L, Hasnain SZ, Fassett RG, McGuckin M, Croci I, Coombes JS. Ramos JS, et al. Diabetes Metab Syndr Obes. 2020 Jul 9;13:2443-2453. doi: 10.2147/DMSO.S251567. eCollection 2020. Diabetes Metab Syndr Obes. 2020. PMID: 32765023 Free PMC article.
Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium.
Corb Aron RA, Abid A, Vesa CM, Nechifor AC, Behl T, Ghitea TC, Munteanu MA, Fratila O, Andronie-Cioara FL, Toma MM, Bungau S. Corb Aron RA, et al. Microorganisms. 2021 Mar 17;9(3):618. doi: 10.3390/microorganisms9030618. Microorganisms. 2021. PMID: 33802777 Free PMC article. Review.
Interleukin-24 as a Pulmonary Target Cytokine in Bronchopulmonary Dysplasia.
Gao R, Li Z, Ai D, Ma J, Chen C, Liu X. Gao R, et al. Cell Biochem Biophys. 2021 Jun;79(2):311-320. doi: 10.1007/s12013-021-00968-z. Epub 2021 Mar 8. Cell Biochem Biophys. 2021. PMID: 33683657
Feasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity.
Sattler FR, Mert M, Sankaranarayanan I, Mack WJ, Galle-Treger L, Gonzalez E, Baronikian L, Lee K, Jahani PS, Hodis HN, Dieli-Conwright C, Akbari O. Sattler FR, et al. PLoS One. 2020 Sep 3;15(9):e0237496. doi: 10.1371/journal.pone.0237496. eCollection 2020. PLoS One. 2020. PMID: 32881912 Free PMC article.
The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues.
Wada Y, Ikemoto T, Morine Y, Imura S, Saito Y, Yamada S, Shimada M. Wada Y, et al. Sci Rep. 2019 Sep 13;9(1):13204. doi: 10.1038/s41598-019-49701-0. Sci Rep. 2019. PMID: 31519950 Free PMC article.

See all "Cited by" articles

References

1. Annu Rev Biochem. 2012;81:767-93 - PubMed
1. Nat Immunol. 2012 Oct;13(10):947-53 - PubMed
1. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8885-90 - PubMed
1. Cell. 2012 Mar 16;148(6):1160-71 - PubMed
1. Cell. 2014 Jul 31;158(3):534-48 - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- Mouse Genome Informatics (MGI)
Miscellaneous
- NCI CPTAC Assay Portal

[1] Annu Rev Biochem. 2012;81:767-93 - PubMed

[2] Annu Rev Biochem. 2012;81:767-93 - PubMed

[3] Nat Immunol. 2012 Oct;13(10):947-53 - PubMed

[4] Nat Immunol. 2012 Oct;13(10):947-53 - PubMed

[5] Proc Natl Acad Sci U S A. 2011 May 24;108(21):8885-90 - PubMed

[6] Proc Natl Acad Sci U S A. 2011 May 24;108(21):8885-90 - PubMed

[7] Cell. 2012 Mar 16;148(6):1160-71 - PubMed

[8] Cell. 2012 Mar 16;148(6):1160-71 - PubMed

[9] Cell. 2014 Jul 31;158(3):534-48 - PubMed

[10] Cell. 2014 Jul 31;158(3):534-48 - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress

Affiliations

Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress

Authors

Affiliations

Abstract

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous

Abstract

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous