Signalling mechanisms linking hepatic glucose and lipid metabolism

Weickert, Martin O.; Pfeiffer, Andreas F. H.

doi:10.1007/s00125-006-0295-3

Cited by 106 publications

(94 citation statements)

References 126 publications

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“…The definition of coordinated changes in plasma metabolites and gene expression could help test causal relationships between insulin resistance and NAFLD. Hepatic insulin-and glucose-responsive metabolic systems play a central role in the regulation of carbohydrate and lipid metabolism [22]. Interpretation of gene expression profiling data relies on mechanistic models integrating molecular markers of disease onset and progression, which derive from clinical and experimental observations.…”

Section: Discussionmentioning

confidence: 99%

“…SREBF1c is a transcription factor involved in carbohydrate and lipid metabolism [8]. Its activation, which simulates lipogenic enzymes in the liver, is mediated by increased glucose and insulin concentrations [22,26]. In fat-fed 129S6 mice, hyperglycaemia and hyperinsulinaemia could directly result in the upregulation of Srebf1c transcription, which can in turn enhance the transcription of Abca1, encoding an Apo-A1 binding protein controlling cholesterol efflux [27].…”

Section: Discussionmentioning

confidence: 99%

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Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

et al. 2007

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Aims/hypothesis Complex changes in gene expression are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD) promoted by feeding a high-fat diet (HFD). We used functional genomic technologies to document molecular mechanisms associated with dietinduced NAFLD. Materials and Methods Male 129S6 mice were fed a diet containing 40% fat (high-fat diet, HFD) for 15 weeks. Glucose tolerance, in vivo insulin secretion, plasma lipid profile and adiposity were determined. Plasma metabonomics and liver transcriptomics were used to identify changes in gene expression associated with HFD-induced NAFLD.Results In HFD-fed mice, NAFLD and impaired glucose and lipid homeostasis were associated with increased hepatic transcription of genes involved in fatty acid uptake, intracellular transport, modification and elongation, whilst genes involved in beta-oxidation and lipoprotein secretion were, paradoxically, also upregulated. NAFLD developed despite strong and sustained downregulation of transcription of the gene encoding stearoyl-coenzyme A desaturase 1 (Scd1) and uncoordinated regulation of transcription of Scd1 and the gene encoding sterol regulatory element binding factor 1c (Srebf1c) transcription. Inflammatory mechanisms appeared to be stimulated by HFD. Conclusions/interpretation Our results provide an accurate representation of subtle changes in metabolic and gene expression regulation underlying disease-promoting and compensatory mechanisms, collectively contributing to dietinduced insulin resistance and NAFLD. They suggest that proposed models of NAFLD pathogenesis can be enriched with novel diet-reactive genes and disease mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

et al. 2007

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“…Thus, AMPK is now recognized as a promising drug target for the treatment of T2DM. There is a strong correlation between AMPK/PGC-1α signaling pathway and T2DM (Weickert & Pfeiffer 2006). For instance, metformin, one of the most widely prescribed drugs for T2DM, exerts a strong antihyperglycemic effect partly though the increasing of PGC-1α expression, via its upstream kinase AMPK (Aatsinki et al 2014).…”

Section: Amp-activated Protein Kinasementioning

confidence: 99%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

132

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Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

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“…Both insulin resistance and diabetes can adversely affect the course of chronic hepatitis C (CHC), leading to enhanced steatohepatitis and liver fibrosis [30][31][32] . Insulin resistance, associated with type 2 diabetes, can promote fatty liver, and excessive hepatic accumulation of fat may promote insulin resistance and therefore contribute to the pathogenesis of the metabolic syndrome [33] . Insulin resistance is a critical component of type 2 diabetes mellitus pathogenesis.…”

Section: Resistancementioning

confidence: 99%

Hepatitis C virus infection and insulin resistance

Bose¹

2014

WJD

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Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is the primary cause for liver transplantation in the western world. Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of type Ⅱ diabetes. Insulin resistance plays an important role in the development of various complications associated with HCV infection. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral treatment. Thus, HCV associated insulin resistance is a therapeutic target at any stage of HCV infection. HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway. Various mechanisms have been proposed in regard to HCV mediated insulin resistance, involving up regulation of inflammatory cytokines, like tumor necrosis factor-α, phosphorylation of insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of lipid droplets. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Hepatitis C virus; Insulin resistance; Insulin receptor substrate 1; Protein kinase B; mammalian target of rapamycin/S6K1; Suppressor of cytokine signaling 3; Glucose transporter-4; Lipid metabolism; Antiviral therapy Core tip: Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection and often leads to development of type Ⅱ diabetes. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, hepatocellular carcinoma and resistance to anti-viral treatment. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways.Bose SK, Ray R. Hepatitis C virus infection and insulin resistance. World J Diabetes 2014; 5(1): 52-58 Available from: URL:

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Signalling mechanisms linking hepatic glucose and lipid metabolism

Cited by 106 publications

References 126 publications

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Hepatitis C virus infection and insulin resistance

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