Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes

Hernández, Rosario; Teruel, Teresa; Lorenzo, Margarita

doi:10.1007/s00125-003-1236-z

Cited by 33 publications

(30 citation statements)

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“…The fact that three unrelated ligands produced similar restoration of glucose uptake seems to indicate that their effects are dependent on NR1HR. Moreover, RAR activation also restored insulin sensitivity in the presence of the cytokine, while the PPARγ agonist rosiglitazone stimulated glucose uptake under basal conditions and produced insulin sensitisation regardless of whether TNFα was present or not, in agreement with previous findings in this cellular model [19,22]. In contrast, RXR activation failed to regulate glucose uptake in all the experimental conditions tested.…”

Section: Discussionsupporting

confidence: 90%

“…1a). We used the following dosages: rosiglitazone as PPARγ agonist, 10 μmol/l, a dose previously used in brown adipocytes [19]; TTNPB as RAR agonist, 10 μmol/l; and phytanic acid as RXR agonist, 20 μmol/l. The latter two doses are similar to those used in other studies in vitro [27].…”

Section: Resultsmentioning

confidence: 99%

“…PTPN1 activity was assessed by malachite green and p-nitrophenyl phosphate hydrolysis assays by dephosphorylation of specific phosphopeptides (Upstate Biotechnology) as previously described by us [19].…”

Section: Methodsmentioning

confidence: 99%

“…In this regard, we decided to explore the expression of PTPN1, as well as of such other lipid and Ser/Thr phosphatases as SHIP2, PTEN or PP2A, all known to be present in brown adipocytes [19]. Therefore, cells were cultured in the absence or presence of TNFα with or without T0910317 for 24 h, and different phosphatases were analysed by western blot (Fig.…”

Section: T0901317 Ameliorates the Insulin Resistance Induced Bymentioning

confidence: 99%

“…Brown adipose tissue is also a target for nuclear receptor agonists, since it produces abundant PPARγ, NR1HRα and β [9,17]. In this regard, the PPARγ agonist rosiglitazone up-regulates the expression of the lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1 genes in brown adipocytes [18], as well as achieving insulin sensitisation by increasing the Tyr kinase activity of the insulin receptor [19]. So far, the effect of activation of NR1HRs on glucose metabolism in brown adipocytes has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

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Aims/hypothesis The nuclear receptors, including nuclear receptor subfamily 1, group H, member 3 (NR1HR, also known as liver X receptor [LXR]), are sensors of cholesterol metabolism and lipid biosynthesis that have recently been proposed as insulin sensitisers. TNFα has been described as a link between obesity and the development of insulin resistance, an important contributor to the pathogenesis of type 2 diabetes. Therefore, we decided to investigate the ability of NR1HR agonists to ameliorate TNFα-induced insulin resistance in brown adipocytes. Methods Primary brown adipocytes from rat fetuses, and from wild-type neonate mice and neonate mice deficient in the gene encoding protein tyrosine phosphatase-1B (Ptpn1, also known as Ptp1b) were cultured in the absence or presence of TNFα and different nuclear receptor agonists. Among them, the unrelated NR1HR ligands T0901317, GW3965 and (22R)-hydroxycholesterol were tested. After insulin stimulation, glucose uptake and solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4) translocation were measured. Next the insulin signalling cascade was determined by submitting cells to lysis, immunoprecipitation and immunoblotting. Results NR1HR agonists ameliorate TNFα-induced insulin resistance restoring completely insulin-stimulated glucose uptake and SLC2A4 translocation to plasma membrane. This effect is parallel to the recovery of the insulin cascade insulin receptor/IRS-2/phosphatidylinositol 3-kinase/protein kinase B, and could be due to the fact that T0901317 prevents the increase of PTPN1 production and phosphatase activity produced by TNFα. In this regard, Ptpn1-deficient brown adipocytes showed protection against insulin resistance by TNFα. Moreover, we observed that T0901317 produced in itself a significant increase over basal glucose uptake consistent with an increase of SLC2A4 protein content in plasma membrane, attributable to the activation of protein kinase ζ and/or the increase of Slc2a4 expression. Conclusions/interpretation Nuclear receptors NR1HR are interesting potential targets for drug treatment of insulin resistance. Keywords

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: T0901317 Ameliorates the Insulin Resistance Induced Bymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

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Rosiglitazone, a PPARγ agonist, ameliorates palmitate‐induced insulin resistance and apoptosis in skeletal muscle cells

Meshkani

Sadeghi

Taheripak

et al. 2014

Cell Biochemistry & Function

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Saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis. Strategies for preventing the cytotoxic effect of palmitate are useful in reduction of diabetes complications. In this study, we introduced RSG as an agent that protects skeletal muscle cells against palmitate-induced apoptosis and insulin resistance. It appears that RSG protects skeletal muscle cells against palmitate-induced apoptosis via the PPARγ-dependent and PTP1B-independent mechanisms. Given the role of FFAs in skeletal muscle apoptosis, these findings support the idea that RSG can ameliorate diabetes complications such as skeletal muscle loss.

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Current literature in diabetes

2004

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 Intervention: a) General; b) Pharmacology; 9 Pathology: a) General; b) Cardiovascular; c) Neurological; d) Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (6 Weeks journals ‐ Search completed at 5th May 2004)

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Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes

Abstract: At the insulin receptor level, rosiglitazone-induced improvements of insulin sensitivity result from two convergent mechanisms: increased insulin receptor expression and insulin receptor activation.

Cited by 33 publications

References 47 publications

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Rosiglitazone, a PPARγ agonist, ameliorates palmitate‐induced insulin resistance and apoptosis in skeletal muscle cells

Current literature in diabetes

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