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β-Cell Dysfunction, Hepatic Lipid Metabolism, and Cardiovascular Health in Type 2 Diabetes: New Directions of Research and Novel Therapeutic Strategies

Lookup NU author(s): Dr Ahmad Al-Mrabeh

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes mellitus (T2DM), and dyslipidemia is one of the main drivers for both metabolic diseases. In this review, the major pathophysiological and molecular mechanisms of β-cell dysfunction and recovery in T2DM are discussed in the context of abnormal hepatic lipid metabolism and cardiovascular health. (i) In normal health, continuous exposure of the pancreas to nutrient stimulus increases the demand on β-cells. In the long term, this will not only stress β-cells and decrease their insulin secretory capacity, but also will blunt the cellular response to insulin. (ii) At the pre-diabetes stage, β-cells compensate for insulin resistance through hypersecretion of insulin. This increases the metabolic burden on the stressed β-cells and changes hepatic lipoprotein metabolism and adipose tissue function. (iii) If this lipotoxic hyperinsulinemic environment is not removed, β-cells start to lose function, and CVD risk rises due to lower lipoprotein clearance. (iv) Once developed, T2DM can be reversed by weight loss, a process described recently as remission. However, the precise mechanism(s) by which calorie restriction causes normalization of lipoprotein metabolism and restores β-cell function are not fully established. Understanding the pathophysiological and molecular basis of β-cell failure and recovery during remission is critical to reduce β-cell burden and loss of function. The aim of this review is to highlight the link between lipoprotein export and lipid-driven β-cell dysfunction in T2DM and how this is related to cardiovascular health. A second aim is to understand the mechanisms of β-cell recovery after weight loss, and to explore new areas of research for developing more targeted future therapies to prevent T2DM and the associated CVD events.


Publication metadata

Author(s): Al-Mrabeh A

Publication type: Review

Publication status: Published

Journal: Biomedicines

Year: 2021

Volume: 9

Issue: 2

Online publication date: 23/02/2021

Acceptance date: 17/02/2021

ISSN (electronic): 2227-9059

URL: https://doi.org/10.3390/biomedicines9020226

DOI: 10.3390/biomedicines9020226


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