The Links of Ghrelin to Incretins, Insulin, Glucagon, and Leptin After Bariatric Surgery.

Daria Skuratovskaia,Elena Kirienkova,Pavel Zatolokin,Aleksandra Komar,Maria Vulf,Egor Shunkin,Nataliya Chasovskikh,Larisa Litvinova

doi:10.3389/fgene.2021.612501

Daria Skuratovskaia, Elena Kirienkova + Show 6 more

Open Access

https://doi.org/10.3389/fgene.2021.612501

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Abstract

Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems. The present study aimed to identify the mechanisms of interaction of critical regulators of carbohydrate metabolism using bioinformatics and experimental methods and to assess their influence on the development of T2DM. We conducted an in silico search for the relationship of hormones and adipokines and performed functional annotation of the receptors for ghrelin and incretins. Hormones and adipokines were assessed in the plasma of obese patients with and without T2DM as well as after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) surgeries. Incretin- and ghrelin-associated functions and metabolic processes were discovered. Low ghrelin levels were observed in obese patients without T2DM compared with healthy volunteers and the other groups. The highest ghrelin levels were observed in obese patients with T2DM. This defense mechanism against insulin resistance could be realized through the receptors G-protein-coupled receptor (GPCR), growth hormone secretagogue receptor (GHSR), and growth hormone-releasing hormone receptor (GHRHR). These receptors are associated with proliferative, inflammatory, and neurohumoral signaling pathways and regulate responses to nutrient intake. Signaling through the GPCR class unites ghrelin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide (GLP)-1. Ghrelin impairs carbohydrate and lipid metabolism in obese patients. Ghrelin is associated with elevated plasma levels of insulin, glucagon, and leptin. Specific activation of receptors and modulation by posttranslational modifications of ghrelin can control IR’s development in obesity, which is a promising area for research.

Highlights

Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems (Dedov et al, 2017; Statistics About Diabetes | ADA, 2020)
The present study aimed to identify the mechanisms of interaction of critical regulators of carbohydrate metabolism using bioinformatics and experimental methods, and to assess their influence on the development of T2DM complicated by obesity
We observed a disturbance in carbohydrate and lipid metabolism parameters in obese patients with T2DM (Supplementary Table 1)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems (Dedov et al, 2017; Statistics About Diabetes | ADA, 2020). T2DM is characterized by the impaired metabolic response of insulin-dependent tissue [e.g., muscle, adipose tissue (AT), liver] to insulin, The Ghrelin After Bariatric Surgery which leads to an increase in its concentration in human plasma (Finan et al, 2013). It is known that gastroduodenal zone hormones and mediators of AT, namely, adipokines, regulate carbohydrate metabolism components and play an important role in the pathogenesis of IR in T2DM (Finan et al, 2013; Vejrazkova et al, 2017). Fasting plasma ghrelin level increases, ghrelin activates gluconeogenesis in the liver, suppresses insulin production, and maintains glucose levels within control parameters. Postprandial hormone production decreases when there is a glucose-stimulated increase in insulin secretion

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