Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

Parvaiz, Fahed; Manzoor, Sobia; Iqbal, Jawed; Sarkar-Dutta, Mehuli; Imran, Muhammad; Waris, Gulam

doi:10.3748/wjg.v21.i43.12361

Cited by 26 publications

(20 citation statements)

References 44 publications

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“…Both fat accumulation and hepatosteatosis have been related to elevations of serum aminotransferase levels in HCV infections rather than DM. It has been reported that nonstructural protein 5A (NS5A) encoded by the HCV RNA genome is involved in insulin receptor substrate-1 (IRS-1) phosphorylation and regulates the insulin signaling pathway [3]. In addition, NS5A transfected cells, decreased the levels of serin phosphorylation that facilitate gluconeogenesis, and inhibited the synthesis of glycogen.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Chronic Hepatitis C Can Improve Glycemic Control in Patients with Type 2 Diabetes

Okuroğlu

Sertbaş

Özdemir

2018

Case Reports in Hepatology

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A 73-year-old female patient with a history of type 2 DM for seven years was admitted to our out-patient clinic with a complaint of frequent hypoglycemic episodes. She was receiving basal- bolus insulin treatment. She underwent liver transplantation 20 months ago due to end stage liver disease caused by HCV infection genotype 1b. While she was still on tacrolimus for liver transplantation, she received direct acting antiviral agents including fix dose ledipasvir-sofosbuvir with ribavirin. Biochemical analysis showed fasting plasma glucose of 105 mg/dl and postprandial glucose of 200 mg/dl, glycosylated hemoglobin A1c of 4.8%, and c-peptide of 3.17 ng/ml. After achieving successfully virologic response with antiviral therapy, the patient stayed euglycemic and was no longer in need to any medication including insulin and the patient was followed only by dietary regulation. Achievement of the virological response in treatment of HCV infection can improve not only the liver status, but also the extrahepatic manifestations including type 2 DM.

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Section: Discussionmentioning

confidence: 99%

Treatment of Chronic Hepatitis C Can Improve Glycemic Control in Patients with Type 2 Diabetes

Okuroğlu

Sertbaş

Özdemir

2018

Case Reports in Hepatology

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“…Several studies in vertebrates have shown that the expression of some genes encoding metabolic enzymes increases significantly during a viral infectious process (Kuo et al., ; Parvaiz et al., ). Nevertheless, little is known about the specific molecular mechanisms affecting the metabolism of key enzymes involved in energy metabolism in shrimp species by viral pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies in vertebrates have shown that the expression of some genes encoding metabolic enzymes increases significantly | 5591 during a viral infectious process (Kuo et al, 2014;Parvaiz et al, 2015 (Chen et al, 2011). Subsequently, Su et al (2014) found a significant increase in several markers of various meta- suggested by the inhibition of PK (Chen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profile of pyruvate kinase and pancreatic lipase encoding mRNAs of the Pacific whiteleg shrimpPenaeus vannameiduring PstDV-1 infection

et al. 2017

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Beyond their ability to infect and spread, viruses lack the ability to replicate by their own. To counter this, viruses have evolved strategies to exploit the host's machinery for the production of new virions. However, viruses are by no means merely passive consumers of host metabolic products. Viruses induce remarkable changes in their host's cellular metabolism, yielding a metabolic state, to meet its specific requirements. The decapod penstyldensovirus (PstDV‐1) is probably the most prevalent virus affecting shrimp farming and has been associated with massive mortality outbreaks in hatchery‐reared larvae and juveniles of Penaeus stylirostris, and results in developmental deformities in symptomatic specimens of P. vannamei. Previous studies have suggested that PstDV‐1 induces metabolic reprogramming of P. vannamei to achieve a successful replication. In this study, the effects of PstDV‐1 infection over the gene expression of pyruvate kinase and pancreatic lipase of the shrimp P. vannamei were evaluated. The expression of both genes was significantly altered by PstDV‐1 infection, which may lead to the accumulation of specific metabolites, as lactate and fatty acids, providing a suitable platform for viral assembly and replication. The transcriptional profile of pyruvate kinase and pancreatic lipase‐encoding mRNAs offers initial clues on the potential metabolic alteration that contribute to PstDV‐1 pathogenesis.

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“…Other studies have also shown that HCV infection can cause insulin resistance by the phosphorylation of IRS-1 at a serine residue (Ser307) followed by a decreased phosphorylation of Akt Thr(308), Fox01 Ser(256) and GSK3β Ser(9), downstream players in the insulin signaling pathway[72,73]. These data raise the question whether insulin resistance is the cause of liver steatosis in patients with chronic HCV infection, or the consequence of viral molecular expression.…”

Section: Insulin Resistance and Hcv Infectionmentioning

confidence: 99%

PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis

Awad

Gassama‐Diagne

2017

WJH

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Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol (PtdIns) 4-kinases, and their lipid products PtdIns(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase (SHIP2), phosphoinositide 3-kinase (PI3K) and their lipid products PtdIns(3,4)P2 and PtdIns(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.

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Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

Abstract: Taken together, our results suggest the role of HCV NS5A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.

Cited by 26 publications

References 44 publications

Treatment of Chronic Hepatitis C Can Improve Glycemic Control in Patients with Type 2 Diabetes

Treatment of Chronic Hepatitis C Can Improve Glycemic Control in Patients with Type 2 Diabetes

Transcriptional profile of pyruvate kinase and pancreatic lipase encoding mRNAs of the Pacific whiteleg shrimpPenaeus vannameiduring PstDV-1 infection

PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis

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