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Insulin Secretion and the β-Cell 102 Years After the Discovery of the Hormone

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Abstract

Purpose of Review

The discovery of insulin was a true landmark in biomedical research and provided a framework for the understanding of many pivotal mechanisms in cell biology throughout the twentieth century, as insulin for instance was the first major protein to have its amino acid sequence and 3D structure resolved. The elucidation of the processes that regulate and mediate insulin secretion has also contributed with crucial mechanistic insights on the pathways that lead to both type 1 and type 2 diabetes mellitus. More than 100 years after the discovery of this hormone, an overview of the present knowledge on insulin output from β-cells should be timely to the general researcher interested in the mechanisms that couple glucose stimulation to insulin secretion.

Recent Findings

Although the mechanisms underlying insulin secretion have been exhaustively studied and understood in animal models, the last decades have shown that important differences can be identified compared to human β-cells. Additionally, despite both reactive oxygen species as well as the immune system have been initially implicated in β-cell dysfunction and the progression to diabetes, increasing evidence indicates that both can also have physiological effects for proper insulin secretion.

Summary

Given this background, this brief review focused on discussing various means by which glucose elicits insulin secretion by the β-cells, particularly on the modulatory role of redox balance and inflammation on β-cell function and/or demise, also drawing attention to the specific mechanisms connecting glucose stimulation to insulin secretion in humans.

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Data and Material Availability

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Code Availability

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Abbreviations

ATF6:

Activating transcription factor 6

BK:

Big potassium, large conductance calcium-activated potassium channel

C3a:

Complement component 3 fragment a

ER:

Endoplasmic reticulum

GLP-1:

Glucagon-like peptide 1

GLUT:

Glucose transporter

GSIS:

Glucose-stimulated insulin secretion

HVA:

High-voltage-activated calcium channel

IAPP:

Islet amyloid polypeptide

IFN-γ:

Interferon-γ

IKK:

Inhibitor of NF-κB kinase

IL-1β:

Interleukin-1β

IL-1R1:

IL-1β receptor 1

IRE1α:

Inositol-requiring enzyme 1 α

JNK:

Jun N-terminal kinase

KATP :

ATP-sensitive potassium channel

Kir6.2:

Inward rectifier potassium channel 6.2 isoform

LVA:

Low voltage-activated calcium channel

MIF:

Macrophage migration inhibitory factor

Nav:

Voltage-dependent sodium channel alpha subunit

NF-κB:

Nuclear factor kappa B

NOD:

Non-obese diabetic

PDI:

Protein disulfide isomerase

PERK:

Protein kinase RNA-like ER kinase

PKR:

Protein kinase R

ROS:

Reactive oxygen species

SUR1:

Sulphonylurea receptor 1

T1D:

Type 1 diabetes mellitus

T2D:

Type 2 diabetes mellitus

TNF:

Tumor necrosis factor

UPR:

Unfolded protein response

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Acknowledgements

Thanks are due to Prof. Patrik Rorsman, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK, for permission to use data in Fig. 1 obtained in his laboratory by FA.

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Author notes

  1. Fernanda Ortis and Eduardo Rebelato contributed equally to the work.

Authors and Affiliations

  1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, 05508-000, Brazil

    Fernanda Ortis

  2. Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, 13083-861, Brazil

    Fernanda Ortis & Fernando Abdulkader

  3. Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, 04023-062, Brazil

    Eduardo Rebelato

  4. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, 05508-000, Brazil

    Angelo Rafael Carpinelli & Fernando Abdulkader

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  1. Fernanda Ortis
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  2. Eduardo Rebelato
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  3. Angelo Rafael Carpinelli
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  4. Fernando Abdulkader
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F.O., E.R., A.R.C. and F.A. wrote, reviewed, edited and approved this manuscript.

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Correspondence to Fernando Abdulkader.

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The animal procedures leading to the results described presented in Fig. 1 were carried out according to national and institutional guidelines of the University of Oxford, UK.

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Ortis, F., Rebelato, E., Carpinelli, A.R. et al. Insulin Secretion and the β-Cell 102 Years After the Discovery of the Hormone. Curr Mol Bio Rep (2024). https://doi.org/10.1007/s40610-024-00158-9

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