Inhibitory effect of tumor necrosis factor α on gluconeogenesis in perfused rat liver

Rocha, Aline Franco da; Liboni, Thaís Fernanda; Moreira, Carolina Campos Lima; Miksza, Daniele Romani; Souza, Camila Oliveira de; Silva, Flaviane de Fatima; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; Souza, Helenir Medri de

doi:10.1007/s11010-012-1531-4

Cited by 6 publications

(4 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF is reported to inhibit hepatic gluconeogenesis prior to pyruvate carboxylase enzymatic step in vivo (63). Circulating levels of TNF were found to be elevated in both Ghr‐ 391 −/− and Ghr −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Loss of growth hormone–mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity

et al. 2019

View full text Add to dashboard Cite

Growth hormone (GH) has an important function as an insulin antagonist with elevated insulin sensitivity evident in humans and mice lacking a functional GH receptor (GHR). We sought the molecular basis for this sensitivity by utilizing a panel of mice possessing specific deletions of GHR signaling pathways. Metabolic clamps and glucose homeostasis tests were undertaken in these obese adult C57BL/6 male mice, which indicated impaired hepatic gluconeogenesis. Insulin sensitivity and glucose disappearance rate were enhanced in muscle and adipose of mice lacking the ability to activate the signal transducer and activator of transcription (STAT)5 via the GHR (Ghr‐391−/−) as for GHR‐null (GHR−/−) mice. These changes were associated with a striking inhibition of hepatic glucose output associated with altered glycogen metabolism and elevated hepatic glycogen content during unfed state. The enhanced hepatic insulin sensitivity was associated with increased insulin receptor β and insulin receptor substrate 1 activation along with activated downstream protein kinase B signaling cascades. Although phosphoenolpyruvate carboxykinase (Pck)‐1 expression was unchanged, its inhibitory acetylation was elevated because of decreased sirtuin‐2 expression, thereby promoting loss of PCK1. Loss of STAT5 signaling to defined chromatin immunoprecipitation targets would further increase lipogenesis, supporting hepatosteatosis while lowering glucose output. Finally, up‐regulation of IL‐15 expression in muscle, with increased secretion of adiponectin and fibroblast growth factor 1 from adipose tissue, is expected to promote insulin sensitivity.—Chhabra, Y., Nelson, C. N., Plescher, M., Barclay, J. L., Smith, A. G., Andrikopoulos, S., Mangiafico, S., Waxman, D. J., Brooks, A. J., Waters, M. J. Loss of growth hormone‐mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity. FASEB J. 33, 6412–6430 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of growth hormone–mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Mice ( N = 6) were anesthetized with isoflurane and the livers were perfused (Da Rocha et al . , ). The perfusion fluid was Krebs–Henseleit buffer (KHB) (Teknova, Hollister, Ca, USA) pH 7.4, 37 °C, saturated with a 95% O 2 , 5% CO 2 combination.…”

Section: Methodsmentioning

confidence: 99%

3,5‐diiodothyronine (3,5‐T2) reduces blood glucose independently of insulin sensitization in obese mice

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This assay was performed as described by Da Rocha et al. , . Briefly, the animals were anesthetized by an i.p.…”

Section: Methodsmentioning

confidence: 99%

Thyroid hormone treatment decreases hepatic glucose production and renal reabsorption of glucose in alloxan-induced diabetic Wistar rats

et al. 2016

View full text Add to dashboard Cite

The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan‐induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Adult Male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 μg/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

show abstract

Inhibitory effect of tumor necrosis factor α on gluconeogenesis in perfused rat liver

Cited by 6 publications

References 43 publications

Loss of growth hormone–mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity

Loss of growth hormone–mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity

3,5‐diiodothyronine (3,5‐T2) reduces blood glucose independently of insulin sensitization in obese mice

Thyroid hormone treatment decreases hepatic glucose production and renal reabsorption of glucose in alloxan-induced diabetic Wistar rats

Contact Info

Product

Resources

About