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Role of microRNAs in regulation of insulin secretion and insulin signaling involved in type 2 diabetes mellitus

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Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder due to insulin resistance that can be caused by both genetic and environmental factors. In 2018, the American Diabetes Association (ADA) estimated more than 500 million T2DM cases globally. In recent years, studies conducted on humans and animals have suggested that non-coding RNAs, namely, microRNAs (miRNAs), post-transcriptionally regulate gene expression that can bring changes in normal physiology, resulting in the development of metabolic diseases. miRNAs also regulate different cellular processes including insulin synthesis and its secretion from pancreatic β-islet cells, its development and function, insulin signaling and glucose homeostasis. Dysregulation of miRNA can affect the functioning of different tissues during the progression of T2DM. This review focuses on various miRNAs that influence the development of β-cells and insulin secretion, various protein cascades that play an important role in insulin signaling and glucose uptake, and their role in insulin resistance. Similarly, the long noncoding RNAs also known as lncRNAs and their β-cell characteristics involved in T2DM have been discussed. Finally, the significance of miRNAs and their mRNA targets as effective biomarkers and therapeutics in studying the early onset and progression of T2DM have been highlighted.

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Abbreviations

AGO2:

argonaute 2

ANRIL:

antisense RNA present in the INK4

βlinc1:

β-cell long intergenic noncoding RNA 1

Cbl:

casitas B-lineage lymphoma

Cbl/CAP:

Cbl-associated protein

DGCR8:

DiGeorge syndrome critical region 8

GLUT-2:

glucose transporter 2

GLUT 4:

glucose transporter 4

GTP:

guanosine-5′-triphosphate

GSIS:

glucose-stimulated insulin secretion

G6P:

glucose-6-phosphate

IGF-1R:

insulin-like growth factors-1 receptor

INSR:

insulin receptors

IRS 1/2:

insulin receptor substrate 1/2

lncRNAs:

long non-coding RNAs

Meg3:

maternal expressed gene 3

MFN2:

mitofusin 2

PDK1:

3-phosphoinositide-dependent protein kinase-1

PIP2:

phosphatidylinositol 4, 5-bisphosphate

PIP3:

phosphatidylinositol (3, 4, 5)-trisphosphate (Ptdlns (3, 4, 5)P3)

PI3K:

phosphoinositide 3-kinase

PTPN1:

protein tyrosine phosphatase non-receptor type 1

Pre-miRNA:

precursor microRNA

Pri-miRNA:

primary microRNA

PTEN:

phosphatase and tensin homolog

PVT1:

plasmacytoma variant translocation 1 gene

Ran:

Ras-related nuclear protein

RNA pol II/III:

RNA polymerase II/III

RISC:

RNA-induced silencing complex

SUR:

sulfonylurea receptors

TET:

ten-eleven translocation

TRBP:

transactivating response RNA-binding protein

T2DM:

type 2 diabetes mellitus

TUG1:

taurine upregulated gene 1

XPO5:

exportin-5

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Authors and Affiliations

  1. Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603 203, India

    Angel Mendonca, Prabu Thandapani, Priyashree Nagarajan, Sanjana Venkatesh & Sujatha Sundaresan

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  1. Angel Mendonca
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  2. Prabu Thandapani
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  3. Priyashree Nagarajan
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  5. Sujatha Sundaresan
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Correspondence to Sujatha Sundaresan.

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Communicated by Ullas Kolthur-Seetharam.

Corresponding editor: Ullas Kolthur-Seetharam

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Mendonca, A., Thandapani, P., Nagarajan, P. et al. Role of microRNAs in regulation of insulin secretion and insulin signaling involved in type 2 diabetes mellitus. J Biosci 47, 58 (2022). https://doi.org/10.1007/s12038-022-00295-2

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