Aberrant liver insulin receptor isoform a expression normalises with remission of type 2 diabetes after gastric bypass surgery

PloS One
Vinko BesicMark T Hayes

Abstract

Type 2 diabetes mellitus (T2DM) results from a combination of progressive insulin resistance and loss of pancreatic beta cell function and/or mass. Insulin signalling occurs through the insulin receptor, (INSR) which is alternatively spliced into two isoforms: INSRA (-exon 11) and INSRB (+exon 11). Because the INSR isoforms have different functional characteristics, their relative expression ratio has been implicated in the pathogenesis of insulin resistance and T2DM. We studied levels of INSR isoform mRNA in liver samples taken from 46 individuals with or without T2DM at Roux-en-Y (RYGB) surgery, and on average 17 (± 5.6) months later in 16 of the same individuals (8 diabetic and non-diabetic patients). INSRA or INSRB was also overexpressed in HepG2 cells to ascertain their effect on AKT phosphorylation and PCK1 expression as markers of insulin-mediated metabolic signalling. We found the INSRB:A isoform ratio was reduced in individuals with T2DM in comparison to those with normal glucose tolerance and normalised with remission of diabetes. The INSRB:A ratio increased due to a reduction in the alternatively spliced INSRA isoform following remission of diabetes. Overexpressing INSRA isoform in HepG2 hepatoma cells reduced inhibi...Continue Reading

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Citations

Feb 24, 2018·International Journal of Molecular Sciences·Chi-Ming WongMabel Yin-Chun Yau
Feb 10, 2018·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Pongpan TanajakNipon Chattipakorn
Aug 27, 2016·Disease Models & Mechanisms·Sabela Diaz-CastroverdeManuel Benito
Oct 4, 2017·Endocrine Reviews·Antonino BelfioreRiccardo Vigneri
Mar 30, 2021·Diabetes & Metabolism Journal·Anni M Y ZhangJames D Johnson
May 23, 2021·Biochimie·Takahito NakuraShin-Ichiro Takahashi
Nov 30, 2021·Disease Models & Mechanisms·Gemma V Brierley, Robert K Semple
Dec 5, 2021·Chemical Biology & Drug Design·Joshua NathanaelSulistyo Emantoko Dwi Putra

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Methods Mentioned

BETA
gastric bypass
biopsy
blood collection
PCR
Assay

Software Mentioned

Quantity One
7300 Sequence Detection
BioSizing

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