Correction to: Defining the underlying defect in insulin action in type 2 diabetes

Batista, Thiago M.; Haider, Nida; Kahn, C. Ronald

doi:10.1007/s00125-022-05684-8

Cited by 2 publications

(2 citation statements)

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“…When IKK2 becomes activated, it phosphorylates IκBα, the inhibitor of NF-κB, which then becomes ubiquitinated and subsequently degraded. IKK2 is a serine-threonine kinase that is able to phosphorylate serine IRS and thus block signal transmission from insulin receptors into the cell's cytoplasm [94]. This further releases NF-κB for translocation into the nucleus and promotes the transcription of proinflammatory genes.…”

Section: Hepatic Inflammation and Insulin Resistancementioning

confidence: 99%

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Vesković,

Šutulović,

Hrnčić

et al. 2023

CIMB

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The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.

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Section: Hepatic Inflammation and Insulin Resistancementioning

confidence: 99%

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Vesković,

Šutulović,

Hrnčić

et al. 2023

CIMB

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“…In the last decade, genome-wide association studies (GWAs) have revealed the association of specific loci with diseases such as cancers, T2D, and cardiovascular disease [ 6 , 7 , 8 , 9 , 10 , 11 ]. For example, loci involved in the insulin signaling pathway may lead to IR and T2D [ 12 , 13 ]. The AKT protein is composed of 480 amino acid residues and comprises three domains: the pleckstrin homology (PH), middle catalytic (kinase) domain, and regulatory C-terminal disordered tail (C-tail) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes

Elangeeb,

Elfaki,

Elkhalifa

et al. 2023

CIMB

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Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein–protein interaction, and large-scale case–control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment.

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Correction to: Defining the underlying defect in insulin action in type 2 diabetes

Cited by 2 publications

References 0 publications

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes

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