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Posttranslational modifications in diabetes: Mechanisms and functions

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Abstract

As one of the most widespread chronic diseases, diabetes and its accompanying complications affect approximately one tenth of individuals worldwide and represent a growing cause of morbidity and mortality. Accumulating evidence has proven that the process of diabetes is complex and interactive, involving various cellular responses and signaling cascades by posttranslational modifications (PTMs). Therefore, understanding the mechanisms and functions of PTMs in regulatory networks has fundamental importance for understanding the prediction, onset, diagnosis, progression, and treatment of diabetes. In this review, we offer a holistic summary and illustration of the crosstalk between PTMs and diabetes, including both types 1 and 2. Meanwhile, we discuss the potential use of PTMs in diabetes treatment and provide a prospective direction for deeply understanding the metabolic diseases.

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Fig. 1
Fig. 2

modified by PTMs). PTMs: posttranslational modifications, APCs: antigen-presenting cells, ROS: reactive oxygen species, OS: oxidative stress, ERS: endoplasmic reticulum stress, DN: double-negative cell, DP: double-positive cell, SP: single-positive cell, MHC: major histocompatibility complex

Fig. 3
Fig. 4

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Data Availability

There were no original data used in this manuscript.

Abbreviations

PTM:

Posttranslational modification

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

Arg:

Arginine

PAD:

Peptidyl arginine deiminase

tTG:

Tissue transglutaminase

OGT:

O-GlcNAc transferase

ERS:

Endoplasmic reticulum stress

OS:

Oxidative stress

ER:

Endoplasmic reticulum

ROS:

Reactive oxygen species

IFN:

Interferon

HLA:

Human leukocyte antigen

FFAs:

Free fatty acids

mTECs:

Medullary thymic epithelial cells

DCs:

Dendritic cells

IAAs:

Islet autoantibodies

MHC:

Major histocompatibility complex

ZnT-8:

Zinc transporter-8

IA-2:

Islet antigen-2

ICA69:

Islet cell autoantigen 69

GAD65:

Glutamate decarboxylase 65

IAPP:

Islet amyloid polypeptide

GRP78:

Glucose-regulated Protein 78

AAB:

Autoantibody

Th :

T helper

Lys:

Lysine

Pro:

Proline

Thr:

Threonine

P4Hb:

Prolyl 4-hydroxylase beta

SUMO:

Small ubiquitin-related modifier

Tyr:

Tyrosine

PDX-1:

Pancreatic/duodenal homeobox-1

HNF1A:

Hepatocyte nuclear factor 1 alpha

SENPs:

Sentrin/SUMO-specific proteases

IRF4:

Interferon regulator factor 4

His:

Histidine

Cys:

Cysteine

Phe:

Phenylalanine

PDC-E2:

Pyruvate dehydrogenase complex-E2

Ser:

Serine

FOX:

Forkhead box

O-GlcNAcylation:

O-linked-N-acetylglucosaminylation

UDP-GlcNAc:

N-acetylglucosamine

OGA:

O-GlcNAcase

HBP:

Hexosamine biosynthesis pathway

NeuroD1:

Neurogenic differentiation factor 1

GPR40:

G protein-coupled receptor 40

AKT:

Protein kinase B

IR:

Insulin receptor

IRS:

Insulin receptor substrate

PI3K:

Phosphoinositide 3-kinase

PDK1:

Phosphoinositide-dependent kinase 1

ChREBP:

Carbohydrate responsive element-binding protein

FXR:

Farnesoid X receptor

CRTC2:

Protein (CREB)-regulated transcriptional coactivator 2

PGC-1α:

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha

LXR:

Liver X receptor

SERCA:

Sarco(endo)plasmic reticulum calcium transport ATPase

GlcN:

Glucosamine

SGK1:

Glucocorticoid-induced kinase 1

C/EBP:

CCAAT enhancer-binding protein

GSIS:

Glucose-stimulated insulin secretion

PPARγ:

Peroxisome proliferator–activated receptor γ

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC), China [grant number 81760160]. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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  1. Bin Chen and Jianing Zhong contributed equally to this work.

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  1. Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, 323 National Road, Ganzhou, 341000, Jiangxi, China

    Ang Hu, Haohong Zou, Bin Chen & Jianing Zhong

  2. The First Affiliated Hospital of Gannan Medical University, Ganzhou, China

    Bin Chen

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Hu, A., Zou, H., Chen, B. et al. Posttranslational modifications in diabetes: Mechanisms and functions. Rev Endocr Metab Disord 23, 1011–1033 (2022). https://doi.org/10.1007/s11154-022-09740-x

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  • DOI: https://doi.org/10.1007/s11154-022-09740-x

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