Differences in protein expression, at the basal state and at 2 h of insulin infusion, in muscle biopsies from healthy Arab men with high or low insulin sensitivity measured by hyperinsulinemic euglycemic clamp

Ilham Bettahi; Roopesh Krishnankutty; Morana Jaganjac; Noor Nabeel M Suleiman; Manjunath Ramanjaneya; Jayakumar Jerobin; Shaimaa Hassoun; Meis Alkasem; Ibrahem Abdelhakam; Ahmad Iskandarani; Tareq A Samra; Vidya Mohamed-Ali; Abdul Badi Abou-Samra

doi:10.3389/fendo.2022.1024832

Differences in protein expression, at the basal state and at 2 h of insulin infusion, in muscle biopsies from healthy Arab men with high or low insulin sensitivity measured by hyperinsulinemic euglycemic clamp

Front Endocrinol (Lausanne). 2023 Feb 17:13:1024832. doi: 10.3389/fendo.2022.1024832. eCollection 2022.

Authors

Ilham Bettahi^{1

2}, Roopesh Krishnankutty², Morana Jaganjac³, Noor Nabeel M Suleiman^{1

4}, Manjunath Ramanjaneya^{1

2}, Jayakumar Jerobin^{1

2}, Shaimaa Hassoun¹, Meis Alkasem¹, Ibrahem Abdelhakam¹, Ahmad Iskandarani^{1

2}, Tareq A Samra^{1

2}, Vidya Mohamed-Ali⁵, Abdul Badi Abou-Samra^{1

4}

Affiliations

¹ Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
² Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
³ Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croatia.
⁴ Weill Cornell Medicine-Qatar, Doha, Qatar.
⁵ Anti-doping Laboratory, Doha, Qatar.

Abstract

Background: Skeletal muscle is the main site for insulin-dependent glucose disposal. The hyperinsulinemic euglycemic clamp (HIEC) is the gold standard for the assessment of insulin sensitivity (IS). We have previously shown that insulin sensitivity, measured by HIEC, varied widely among a group of 60 young healthy men with normoglycemia. The aim of this study was to correlate the proteomic profile of skeletal muscles to insulin sensitivity.

Methods: Muscle biopsies from 16 subjects having the highest (M ≥ 13; n = 8, HIS) and lowest (M ¾ 6, n = 8, LIS) IS were obtained at baseline and during insulin infusion after stabilization of the blood glucose level and glucose infusion rate at the end of the HIEC. The samples were processed using a quantitative proteomic analysis approach.

Results: At baseline, 924 proteins were identified in the HIS and LIS groups. Among the 924 proteins detected in both groups, three were suppressed and three were increased significantly in the LIS subjects compared with the HIS subjects. Following insulin infusion, 835 proteins were detected in both groups. Among the 835 proteins, two showed differential responsiveness to insulin; ATP5F1 protein was decreased, and MYLK2 was higher in the LIS group compared with that in the HIS group. Our data suggest that alteration in mitochondrial proteins and an increased number of proteins involved in fast-twitch fiber correlate to insulin sensitivity in healthy young Arab men.

Conclusions: These results suggest a change in a small number of differentially expressed proteins. A possible reason for this small change could be our study cohorts representing a homogeneous and healthy population. Additionally, we show differences in protein levels from skeletal muscle in low and high insulin sensitivity groups. Therefore, these differences may represent early events for the development of insulin resistance, pre-diabetes, and type 2 diabetes.

Keywords: HIEC; diabetes; insulin resistance; insulin sensitivity; mitochondria; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arabs
Biopsy
Diabetes Mellitus, Type 2*
Glucose
Glucose Clamp Technique
Humans
Insulin
Insulin Resistance*
Male
Muscle, Skeletal
Proteomics

Substances

Insulin
Glucose

Associated data

figshare/10.6084/m9.figshare.21988487

Grants and funding

This work was funded by a grant from the Qatar National Research Fund (NPRP-74613117), a member of the Qatar Foundation, Doha, Qatar, and by the Qatar Metabolic Institute of Hamad Medical Corporation.