Glucocorticoids Fail to Cause Insulin Resistance in Human Subcutaneous Adipose Tissue In Vivo

Hazlehurst, Jonathan; Gathercole, Laura; Nasiri, Maryam; Armstrong, Matthew J.; Borrows, Sarah; Yu, Jinglei; Wagenmakers, Anton J. M.; Stewart, Paul M.; Tomlinson, Jeremy W.

doi:10.1210/jc.2012-3523

Cited by 55 publications

(56 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Fig. 7A, there was a slightly higher expression of insulin pathway transcripts including FOXO1, the insulin receptor (INSR), the insulin receptor substrates IRS1 or IRS2 and the p85 regulatory subunit of phosphoinositide-3-kinase (PIK3R1), consistent with previous studies (Gathercole et al 2007, Tomlinson et al 2010, Hazlehurst et al 2013, though in our hands none of these genes reached statistical significance. The insulin pathway was generally expressed at significantly higher levels in the Cushing's disease patients compared to controls (KEGG pathway, net enrichment score 1.84, PadjZ0.006).…”

Section: Genes Controlling Glucose Oxidation Are Elevated In Cushing'supporting

confidence: 91%

“…Glucocorticoid-induced insulin resistance is thought to be mostly secondary to the increase in free fatty acids caused by the induction of lipolysis (Geer et al 2014). Results from a recent study imply that glucocorticoids do not induce insulin resistance in subcutaneous adipose tissue in vivo in healthy subjects (Hazlehurst et al 2013), suggesting that peripheral insulin resistance may not occur in adipocytes and that whole-body insulin resistance may primarily occur in muscle and liver tissues. This is consistent with our observations of a lack of changes in proximal insulin signaling transcripts (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Hochberg

Harvey

Tran

et al. 2016

EJEA

View full text Add to dashboard Cite

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (nZ5) compared to patients with nonfunctioning pituitary adenomas (nZ11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.

show abstract

Section: Genes Controlling Glucose Oxidation Are Elevated In Cushing'supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Hochberg

Harvey

Tran

et al. 2016

EJEA

View full text Add to dashboard Cite

show abstract

“…Indeed, GC binding to tissue homogenates and GR mRNA expression is higher in omental fat than in SAT (67,68). Moreover, GCs were able to induce insulin resistance in human omental but not in subcutaneous adipocytes (69). In humans, GC excess results in increased abdominal VAT deposition and reduced peripheral subcutaneous adipose depots.…”

Section: Gcs and Obesitymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

View full text Add to dashboard Cite

Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

show abstract

“…While in isolation they decrease lipogenesis, in combination with insulin they act synergistically to increase lipid accumulation (67). They also have profound effects on adipose tissue to drive lipolysis as well as adipocyte differentiation.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

show abstract

Glucocorticoids Fail to Cause Insulin Resistance in Human Subcutaneous Adipose Tissue In Vivo

Cited by 55 publications

References 34 publications

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Metabolic comorbidities in Cushing's syndrome

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Contact Info

Product

Resources

About