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Zlatkina et al. Vessel Plus 2019;3:7 Vessel Plus
DOI: 10.20517/2574-1209.2019.03

Review Open Access

Trigger mechanisms in insulin resistance and
diabetes mellitus development

Vira Zlatkina , Olena Karaya , Natalia Yarmish , Anna Shalimova 4
1
2
3
1 Department of Clinical Pharmacy and Internal Medicine, Kharkiv National Medical University, Kharkiv 61022, Ukraine.
2 Department of General Practice - Family Medicine, Kharkiv National Medical University, Kharkiv 61022, Ukraine.
3 Department of Biochemistry, Kharkiv National Medical University, Kharkiv 61022, Ukraine.
4 The Government Institution “L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”,
Kharkiv 61039, Ukraine.

Correspondence to: Dr. Anna Shalimova, The Government Institution “L.T. Malaya Therapy National Institute of the National
Academy of Medical Sciences of Ukraine”, Kharkiv 61039, Ukraine. E-mail: anna.shalimova83@gmail.com

How to cite this article: Zlatkina V, Karaya O, Yarmish N, Shalimova A. Trigger mechanisms in insulin resistance and diabetes
mellitus development. Vessel Plus 2019;3:7. http://dx.doi.org/10.20517/2574-1209.2019.03

Received: 21 Dec 2018 First Decision: 22 Jan 2019 Revised: 25 Jan 2019 Accepted: 26 Jan 2019 Published: 19 Mar 2019

Science Editor: Alexander N. Orekhov Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Type 2 diabetes mellitus characterized by chronic hyperglycaemia is caused by insulin resistance and β-cell dysfunction.
Glycogen accumulation, due to impaired metabolism, contributes to this “glucotoxicity” via dysregulated biochemical
pathways promoting β-cell dysfunction. Thus, long-term exposition of insulin-secreted cells or isolated islets together
with increased free fatty acids (FFA) and glucose levels can cause insulin-induced glucose secretion depression,
damage to insulin gene expression and apoptotic death of cells. It is known that, the main regulator of pancreatic β-cells
functioning and regulator of insulin gene expression, synthesis and secretion of insulin is glucose. Glucose enters
cells and progressively metabolizes, in particular, to pyruvate in a cycle of tricarboxylic acids, subjected to oxidative
phosphorylation, during which formed adenosine triphosphate and reactive oxygen radicals (ROS). Although, when
more glucose enters the cell, there are other ways in which extra glucose can be transferred to reserve and of the
glucose molecules can form ROS. The release of excessive amounts of FFA leads to lipotoxicity, as lipids and metabolites
produce ROS in the endoplasmic reticulum and mitochondria. This affects both adipose and non-fat tissue, making up
its pathophysiology in many organs. This overview demonstrates that the insulin gene is expressed in pancreatic β-cells.
Glucose is the main physiological regulator of insulin gene expression. It controls the effect of transcription factors, insulin
mRNA stability, and transcription rate. Glucolipotoxicity mechanisms affect the transcription factors MafA and PDX-1.
Important is the β-cells damaging, which is connected with the oxidative stress and the synthesis of ceramides.

Keywords: Diabetes mellitus, insulin resistance, glucotoxicity, lipotoxicity

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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