The Effect of In Vivo Thyroxine Treatment on Insulin Receptors, Glucose Transport and GLUT4 in Rat Adipocytes

Journal of Endocrinology

Klein²,

Krahlisch³

et al. 2003

Tumor necrosis factor (TNF) -induced adipose-related protein (TIARP) has recently been cloned as a TNFstimulated protein expressed in adipocytes. Its expression is differentiation-dependent and potentially involved in mediating TNF -induced insulin resistance. To further characterize regulation of TIARP gene expression, 3T3-L1 adipocytes were treated with key hormones modulating insulin sensitivity and influencing adipocyte metabolism, and TIARP gene expression was determined by quantitative real-time RT-PCR. Interestingly, TIARP mRNA expression was stimulated almost 9-fold after 500 ng/ml GH were added for 16 h whereas addition of 10 µM isoproterenol, 100 nM insulin and 100 nM dexamethasone for 16 h significantly decreased TIARP gene expression to between 35 and 50% of control levels. In contrast, angiotensin 2 (10 µM) and triiodothyronine (1 µM) did not have any effect. The stimulatory effect of GH was time-and dose-dependent with stimulation occurring as early as 1 h after effector addition and at concentrations as low as 5 ng/ml GH. Moreover, pharmacological inhibition of Janus kinase 2 and p42/44 mitogenactivated protein kinase reversed the stimulatory effect of GH, suggesting that both signaling molecules are involved in activation of TIARP gene expression by GH. Furthermore, an increase of TIARP mRNA could be completely reversed to control levels by withdrawal of GH for 24 h. Taken together, these results show that TIARP is not only responsive to TNF but also to important other hormones influencing glucose homeostasis and adipocyte metabolism. Thus, this factor may play an integrative role in the pathogenesis of insulin resistance and its link to obesity.

Section: Discussionmentioning

confidence: 62%

GH is a positive regulator of tumor necrosis factor alpha-induced adipose related protein in 3T3-L1 adipocytes

Journal of Endocrinology

Klein²,

Krahlisch³

et al. 2003

“…Dexamethasone induces insulin resistance at least partly via downregulation of IRS-1 (Turnbow et al 1994). Thyroid hormone-induced insulin resistance is accompanied by decreased expression and translocation of the insulin-responsive glucose transporter-4 (Fickova et al 1997). In our in vitro system, chronic incubation of 3T3-L1 adipocytes with pharmacological doses of dexamethasone, AT2 and T3 does not influence SOCS-3 gene expression.…”

Section: Figurementioning

confidence: 63%

Isoproterenol is a positive regulator of the suppressor of cytokine signaling-3 gene expression in 3T3-L1 adipocytes

Journal of Endocrinology

Klein²,

Lössner³

et al. 2002

SOCS (suppressor of cytokine signaling)-3 has recently been shown to be an insulin-and tumor necrosis factor (TNF)--induced negative regulator of insulin signaling. To further clarify a potential involvement of SOCS-3 in the development of insulin resistance, we measured differentiation-dependent SOCS-3 mRNA expression in 3T3-L1 adipocytes and studied its regulation by various hormones known to impair insulin signaling using quantitative real-time RT-PCR. There was a differentiationdependent downregulation of SOCS-3 mRNA by 50% over the 9 day adipocyte differentiation course. Interestingly, besides insulin and TNF-, chronic treatment of differentiated 3T3-L1 cells with 10 µM isoproterenol for 16 h stimulated SOCS-3 gene expression by about 3·5-fold. Furthermore, isoproterenol stimulated SOCS-3 mRNA expression in a dose-dependent manner with significant activation detectable at concentrations as low as 10 nM isoproterenol. Moreover, a strong 27-and 47-fold activation of SOCS-3 mRNA expression could be seen after 1 h of isoproterenol and GH treatment respectively. The stimulatory effect of isoproterenol could be almost completely reversed by pretreatment of 3T3-L1 cells with the -adrenergic antagonist propranolol. Finally, isoproterenol's action could be mimicked by stimulation of G S -proteins with cholera toxin and of adenylyl cyclase with forskolin and dibutyryl cAMP. Taken together, our results demonstrate a differentiation-dependent downregulation of SOCS-3 in adipocytes and suggest that SOCS-3 gene expression is stimulated by -adrenergic agents via activation of a G S -protein-adenylyl cyclasedependent pathway. As SOCS-3 is a novel inhibitor of insulin signaling, the data support a possible role of this protein as a selectively regulated mediator of catecholamine-induced insulin resistance.

“…Increased serum levels of thyroid hormones, AT2 or GH have also been shown to impair glucose tolerance profoundly (29)(30)(31). In our in vitro system, none of these hormones affect galectin-12 gene expression.…”

Section: Discussionmentioning

confidence: 74%

Negative regulation of adipose-expressed galectin-12 by isoproterenol, tumor necrosis factor alpha, insulin and dexamethasone

European Journal of Endocrinology

Klein²,

Lössner³

et al. 2002

Objective: Galectin-12 has recently been shown to be a predominantly adipocyte-expressed protein which is stimulated by insulin-sensitizing thiazolidinediones and possesses apoptosis-inducing activity. Methods: To further clarify galectin-12 regulation and its potential involvement in the development of insulin resistance, 3T3-L1 adipocytes were chronically treated with various hormones known to impair insulin sensitivity, and galectin-12 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Results: Treatment of 3T3-L1 cells for 16 h with 10 mmol/l isoproterenol, 100 nmol/l insulin, 0.6 nmol/l tumor necrosis factor a (TNFa), and 100 nmol/l dexamethasone reduced galectin-12 gene expression between 47% and 85%. These negative effects were dose-dependent with significant inhibition detectable at concentrations as low as 10 nmol/l isoproterenol, 0.06 nmol/l TNFa, and 1 nmol/l dexamethasone. Furthermore, the inhibitory effect of isoproterenol could be almost completely reversed by pretreatment with the b-adrenergic antagonist propranolol and mimicked by stimulation of G S -proteins with cholera toxin or by activation of adenylyl cyclase with forskolin and dibutyryl-cAMP. Conclusions: Our results suggest that galectin-12 is an adipocyte-expressed protein which is downregulated by various insulin resistance-inducing hormones. These findings imply a role for galectin-12 in the pathogenesis of insulin resistance.