Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

Hayat Aljaibeji; Noha Mousaad Elemam; Abdul Khader Mohammed; Hind Hasswan; Mahammad Al Thahyabat; Noura Alkhayyal; Nabil Sulaiman; Jalal Taneera

doi:10.1055/a-1261-5282

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2022; 130(01): 22-29
DOI: 10.1055/a-1261-5282

Article

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

Hayat Aljaibeji‡

¹Sharjah Institute for Medical Research, University of Sharjah

,

Noha Mousaad Elemam‡

¹Sharjah Institute for Medical Research, University of Sharjah

,

Abdul Khader Mohammed

¹Sharjah Institute for Medical Research, University of Sharjah

,

Hind Hasswan

¹Sharjah Institute for Medical Research, University of Sharjah

,

Mahammad Al Thahyabat

²Mediclinic Parkview Hospital, Dubai

,

Noura Alkhayyal

¹Sharjah Institute for Medical Research, University of Sharjah

,

Nabil Sulaiman

³Department of Family Medicine, College of Medicine, University of Sharjah

⁴Baker/IDI Heart and Diabetes Institute, Melbourne, Victoria

,

Jalal Taneera

¹Sharjah Institute for Medical Research, University of Sharjah

⁵Department of Basic Medical Sciences, College of Medicine, University of Sharjah

› Author Affiliations

Abstract

Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

Key words

Diabetes - Autoimmunity - Let7b-5p. - INS-1 (832/31) - miRNA

Full Text

References

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Supplementary Material

Supplementary Material