Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes

Shimomura, Iichiro; Bashmakov, Yuriy K.; Ikemoto, Shinji; Horton, Jay D.; Brown, Michael S.; Goldstein, Joseph L.

doi:10.1073/pnas.96.24.13656

Cited by 694 publications

(588 citation statements)

References 30 publications

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“…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%

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%

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

et al. 2007

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“…In addition to regulation by sterols, increased expression and aberrant regulation of SREBP-1c are associated with diabetes and fatty liver (Shimomura et al 1999b), and enhanced nuclear accumulation of SREBP-1c in the liver by insulin signaling has been known for several years (Horton et al 1998;Kim et al 1998;Shimomura et al 1999a). However, because the amounts of SREBP-1c mRNA and precursor protein were also increased by insulin, whether there was an active effect of insulin on the maturation of SREBP was not clear.…”

Section: Srebp Regulation By Insulinmentioning

confidence: 98%

Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it's been

Osborne

Espenshade²

2009

Genes Dev.

230

249

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Sterol regulatory element-binding proteins (SREBPs) are a subfamily of basic helix–loop–helix leucine zipper (bHLH-LZ) transcription factors that are conserved from fungi to humans and are defined by two key features: a signature tyrosine residue in the DNA-binding domain, and a membrane-tethering domain that is a target for regulated proteolysis. Recent studies including genome-wide and model organism approaches indicate SREBPs coordinate cellular lipid metabolism with other cellular physiologic processes. These functions are broadly related as cellular adaptation to environmental changes ranging from nutrient fluctuations to toxin exposure. This review integrates classic features of the SREBP pathway with newer information regarding the regulation and sensing mechanisms that serve to assimilate different cellular physiologic processes for optimal function and growth.

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“…A report showed that diabetes may decrease both SREBP-2 and HMGCR mRNA in the liver of rats, and insulin partially reversed the alterations induced by diabetes [40] . Insulin is considered to be a potent inducer of HMGCR [41] .…”

Section: Discussionmentioning

confidence: 99%

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Wang

Liu

et al. 2012

Acta Pharmacol Sin

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Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

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Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes

Cited by 694 publications

References 30 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

Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it's been

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

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