Insulin receptor binding motif tagged with IgG4 Fc (Yiminsu) works as an insulin sensitizer to activate Akt signaling in hepatocytes

Wang, J; T, Zou; Yang, Hongbo; Yz, Gong; Xie, Xiao Song; Hy, Liu; Df, Liao

doi:10.4238/2015.august.3.5

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Liver is the most important organ in the regulation of glycometabolism and lipid metabolism (Ding et al, 2018). Generally, insulin binds to the IR and stimulates the autophosphorylation of IR tyrosine residues, which further activates tyrosine kinase in hepatocytes (Brunetti, 2014; Wang et al, 2015). And then tyrosine kinase phosphorylates insulin receptor substrate 1 and 2 (IRS-1 and IRS-2), which can bind to and activate phosphatidylinositol 3-kinase (PI3K).…”

Section: Mechanism Of Hepatic Insulin Resistancementioning

confidence: 99%

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Nie

Huang

et al. 2019

Front. Pharmacol.

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Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid–induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.

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Section: Mechanism Of Hepatic Insulin Resistancementioning

confidence: 99%

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Nie

Huang

et al. 2019

Front. Pharmacol.

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“…Therefore, a better understanding of the mechanism of hepatic IR may help in elucidating a new therapeutic target for the treatment and prevention of diabetes. Insulin binds to the insulin receptor and promotes the autophosphorylation of IR tyrosine residues in the hepatocytes [22,23].…”

Section: Discussionmentioning

confidence: 99%

Berberine improves hepatic insulin resistance by activating the SIRT1/Opa1 pathway: An in vitro and in vivo study

Zhang

et al. 2021

Preprint

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Aim: This study explored whether abnormality in the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) causes hepatic insulin resistance and whether berberine (BBR) can prevent hepatic insulin resistance through the SIRT1/Opa1 pathway. Method: High-fat diet (HFD)-fed mice and db/db mice were used as animal models to study hepatic insulin resistance in vivo . Insulin resistance, morphological changes, and mitochondrial injury of the liver were examined to explore the effects of BBR. SIRT1/Opa1 protein expressions were determined to confirm whether the signalling pathway was damaged in the model animals and involved in BBR treatment. A palmitate (PA)-induced hepatocyte insulin resistance model was established in HepG2 cells in vitro . Opa1 silencing and SIRT1 overexpression were induced to verify whether Opa1 abnormality causes hepatocyte insulin resistance and whether SIRT1 could improve this dysfunction. BBR treatment and SIRT1 silencing were employed to prove that BBR can prevent hepatic insulin resistance by activating the SIRT1/Opa1 pathway. Results: We found that Opa1 deficiency caused imbalance in mitochondrial fusion/fission and impaired insulin signalling in the HepG2 cells. SIRT1 and BBR overexpression ameliorated PA-induced insulin resistance, increased Opa1, and improved mitochondrial function. SIRT1 silencing could partly reverse the effects of BBR in the HepG2 cells. SIRT1 and Opa1 were downregulated in the animal models. BBR attenuated hepatic insulin resistance and enhanced SIRT1/Opa1 signalling in the the db/db mice. Conclusion: Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte insulin resistance. BBR may improve hepatic insulin resistance by regulating the SIRT1/Opa1 pathway, and thus, it may be used to treat type 2 diabetes.

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“…It can improve insulin resistance by activating the AMPK/PI3K/AKT signaling pathway to initiate downstream cascade signals. 165 , 166…”

Section: Igg Fc Fusion Proteinmentioning

confidence: 99%

Research Advances in Fusion Protein-Based Drugs for Diabetes Treatment

Deng,

Zhao,

Zou

et al. 2024

DMSO

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Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels, resulting in multi-organ dysfunction and various complications. Fusion proteins can form multifunctional complexes by combining the target proteins with partner proteins. It has significant advantages in improving the performance of the target proteins, extending their biological half-life, and enhancing patient drug compliance. Fusion protein-based drugs have emerged as promising new drugs in diabetes therapeutics. However, there has not been a systematic review of fusion protein-based drugs for diabetes therapeutics. Hence, we conducted a comprehensive review of published literature on diabetic fusion protein-based drugs for diabetes, with a primary focus on immunoglobulin G (IgG) fragment crystallizable (Fc) region, albumin, and transferrin (TF). This review aims to provide a reference for the subsequent development and clinical application of fusion protein-based drugs in diabetes therapeutics.

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Insulin receptor binding motif tagged with IgG4 Fc (Yiminsu) works as an insulin sensitizer to activate Akt signaling in hepatocytes

Cited by 6 publications

References 24 publications

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

Berberine improves hepatic insulin resistance by activating the SIRT1/Opa1 pathway: An in vitro and in vivo study

Research Advances in Fusion Protein-Based Drugs for Diabetes Treatment

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