Glucocorticoid‐mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle

Salehzadeh, Firoozeh; Al-Khalili, Lubna; Kulkarni, Sameer S.; Wang, Minghan; Lönnqvist, Fredrik; Krook, Anna

doi:10.1002/dmrr.944

Cited by 22 publications

(12 citation statements)

References 47 publications

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“…The pre-receptor metabolism of the glucocorticoids determine the tissue specific sensitivity, which is also partly regulated by enzyme 11β-HSD1 that converts inactive cortisone to active cortisol (Salehzadeh et al, 2009). Increased adipose tissue 11β-HSD expression has been observed in obesity, which may lead to increased local glucocorticoid signaling (Stimson et al, 2009).…”

Section: Role Of 11βhsd1 In Glucocorticoid-mediated Effects On Skeletmentioning

confidence: 99%

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

et al. 2012

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Section: Role Of 11βhsd1 In Glucocorticoid-mediated Effects On Skeletmentioning

confidence: 99%

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

et al. 2012

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“…The induction of PDK4 gene transcription by GR may contribute to GC-regulated glycogen metabolism in myotubes. One report shows that a reduction of the expression of PDK4 in human primary myotubes diminishes GC-repressed glycogen synthesis [143]. Notably, GC also inhibits insulin-stimulated glycogen synthesis and the activity of glycogen synthase [9].…”

Section: Glycogen Metabolismmentioning

confidence: 99%

Regulation of Glucose Homeostasis by Glucocorticoids

Kuo

McQueen

Chen

et al. 2015

Advances in Experimental Medicine and Biology

539

342

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Glucocorticoids are steroid hormones that regulate multiple aspects of glucose homeostasis. Glucocorticoids promote gluconeogenesis in liver, whereas in skeletal muscle and white adipose tissue they decrease glucose uptake and utilization by antagonizing insulin response. Therefore, excess glucocorticoid exposure causes hyperglycemia and insulin resistance. Glucocorticoids also regulate glycogen metabolism. In liver, glucocorticoids increase glycogen storage, whereas in skeletal muscle they play a permissive role for catecholamine-induced glycogenolysis and/or inhibit insulin-stimulated glycogen synthesis. Moreover, glucocorticoids modulate the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin, two hormones that play a pivotal role in the regulation of blood glucose levels. Overall, the major glucocorticoid effect on glucose homeostasis is to preserve plasma glucose for brain during stress, as transiently raising blood glucose is important to promote maximal brain function. In this chapter we will discuss the current understanding of the mechanisms underlying different aspects of glucocorticoid-regulated mammalian glucose homeostasis.

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“…Thus, the induction of Pdk4 plays a critical role in GC-decreased glucose utilization (Sugden and Holness, 2003). Recent studies indicated that, in human primary myotubes, GC–repressed glycogen synthesis is diminished with reduced expression of PDK4 (Salehzadeh et al, 2009). GCs upregulate Pdk4 gene transcription in both liver and skeletal muscle, and GREs of human PDK4 and rat Pdk4 have been identified (Connaughton et al, 2010; Kwon et al, 2004).…”

Section: The Regulation Of Glucose Metabolism By Glucocorticoidsmentioning

confidence: 99%

Metabolic functions of glucocorticoid receptor in skeletal muscle

Kuo

Harris

Wang

2013

Molecular and Cellular Endocrinology

188

144

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Glucocorticoids (GCs) exert key metabolic influences on skeletal muscle. GCs increase protein degradation and decrease protein synthesis. The released amino acids are mobilized from skeletal muscle to liver, where they serve as substrates for hepatic gluconeogenesis. This metabolic response is critical for mammals’ survival under stressful conditions, such as fasting and starvation. GCs suppress insulin-stimulated glucose uptake and utilization and glycogen synthesis, and play a permissive role for catecholamine-induced glycogenolysis, thus preserving the level of circulating glucose, the major energy source for the brain. However, chronic or excess exposure of GCs can induce muscle atrophy and insulin resistance. GCs convey their signal mainly through the intracellular glucocorticoid receptor (GR). While GR can act through different mechanisms, one of its major actions is to regulate the transcription of its primary target genes through genomic glucocorticoid response elements (GREs) by directly binding to DNA or tethering onto other DNA-binding transcription factors. These GR primary targets trigger physiological and pathological responses of GCs. Much progress has been made to understand how GCs regulate protein and glucose metabolism. In this review, we will discuss how GR primary target genes confer metabolic functions of GCs, and the mechanisms governing the transcriptional regulation of these targets. Comprehending these processes not only contributes to the fundamental understanding of mammalian physiology, but also will provide invaluable insight for improved GC therapeutics.

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Glucocorticoid‐mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle

Cited by 22 publications

References 47 publications

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

Regulation of Glucose Homeostasis by Glucocorticoids

Metabolic functions of glucocorticoid receptor in skeletal muscle

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