Abstract
The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.
Highlights
Diabetes mellitus, commonly known as diabetes, is one of the most complex diseases of humankind
Yoshida et al in 2001 [42], demonstrated that Ire1α stimulates X-box-binding protein 1 (XBP1), resulting in downstream signaling, which leads to the generation of a functional transcription factor
This factor was identified as X-box-binding protein 1 splicing (XBP1s), which is responsible for gene up-regulation in the nucleus [43]
Summary
Commonly known as diabetes, is one of the most complex diseases of humankind. Type I diabetes, which accounts for approximately 10% of all diabetes, is a metabolic perturbation in which the immune system targets the pancreatic beta cells responsible for insulin synthesis [4]. Due to these effects, the body cannot produce enough insulin or is unable to produce any at all. Type II diabetes, known as maturity-onset diabetes, is associated with insulin resistance and accounts for approximately 90% of all diabetes [5,6] This condition occurs when the body cells cannot effectively utilize insulin, resulting in hyperglycemia and insulin overproduction [7]. This review provides up-todate information regarding the ER, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting ER stress in type II diabetes
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