Associated factors and principal pathophysiological mechanisms of type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus(T2DM) as a common chronic disease with an increasing prevalence worldwide that poses a great threat to individual health, and is characterized by chronic hyperglycemia resulting from insulin resistance (IR) coupled with β-cell dysfunction. Mitochondrial dysfunction, obesity, gut microbiota, oxidative stress and inflammation have emerged as a significant contributor to the etiology of T2DM, affecting various metabolic processes critical for glucose homeostasis. This short review underscores their role in enhancing T2DM-related molecular mechanisms and explores recent advancements in diabetic management, further highlights the importance of personalized care plans to address the complexities of the T2DM and aims to improve patient quality of life and long-term health outcome.

Keywords: gut microbiota; insulin resistance; mitochondrial function; obesity; pathogenic mechanism; type 2 diabetes mellitus.

Figure 1

(a) illustrates mitochondrial dysfunction (abnormal mitochondrial fusion or excessive mitochondrial fission) triggers mitochondrial fragmentation, anomalous mitophagy, overproduced ROS, reduced ATP synthesis, dysregulated mitochondrial dynamics, further impairs cellular metabolism and contributes to T2DM progression; (b) presents the extracellular environment cues affect mitochondrial biogenesis and dynamics, as dysfunctional mitochondria fail to adapt to changing metabolic demands, leading to cellular dysfunction and T2DM; (c) presents adipocyte-induced obesity is significant in T2DM pathogenesis, and obesity-related dyslipidemia, inflammation and insistent hyperglycemia condition regulate IR through different molecular pathway.

Figure 2

(a) illustrates dysbiosis of gut microbiota is related to LPS-induced inflammatory pathways, as well as BCAAs, SCFAs and BAs disrupt metabolic pathways, eventually triggers IR by impairing the gut mucosal barrier and increasing intestinal permeability; (b) presents inflammatory pathways impacting IR and possible action, and illustrates chronic hyperglycemia, oxidative stress, lipid metabolism and B-cell dysfunction can activate pro-inflammatory pathways, further exacerbate IR in T2DM; (c) presents oxidative stress-induced insulin resistance-related signaling pathways, and summarizes the mitochondrial dysfunction, lipid oxidation, insulin signaling pathway, inflammatory response, as well as its related pathways are instrumental in regulating T2DM.