Decreased insulin binding and antilipolytic response in adipocytes from patients with Cushing's syndrome

1987 ◽  
Vol 7 (9) ◽  
pp. 713-719 ◽  
Author(s):  
C. Calle ◽  
M. C. Carranza ◽  
M. A. Simón ◽  
A. Torres ◽  
P. Mayor
Keyword(s):  
Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Insulin Receptors ◽  
Human Adipose Tissue ◽  
Insulin Binding ◽  
Cushing's Syndrome ◽  
Human Adipocytes ◽  
Receptor Affinity ◽  
Endogenous Regulation

Human adipocytes from patients with chronic endogenous hypercortisolism (Cushing's syndrome) showed a statistically significant decrease in insulin binding at low unlabelled-insulin concentrations but no change in receptor numbers (Cushing's 180,000±48,000 (3) receptors/cell and controls 189,000±30,000 (7)) together with a fourfold decrease in apparent receptor affinity (ED50: Cushing's 2.25×10−9 M and controls 0.57×10−9 M) and a decreased sensitivity to the antilipolytic effect of insulin. These events could represent the final situation of a chronic and endogenous regulation by high levels of cortisol of insulin receptors in human adipose tissue.

Chronic and endogenous regulation of insulin receptors by catecholamines in adipocytes from patients with a phaeochromocytoma

1990 ◽  
Vol 10 (2) ◽  
pp. 201-207 ◽  
Author(s):  
M. C. Carranza ◽  
M. A. Simón ◽  
A. Torres ◽  
C. Calle
Keyword(s):  
Adipose Tissue ◽  
Binding Sites ◽  
Insulin Receptors ◽  
Human Adipose Tissue ◽  
Insulin Binding ◽  
Scatchard Analysis ◽  
Cooperative Model ◽  
Receptor Affinity ◽  
Site Model ◽  
Binding Data

Insulin binding in adipocytes from patients with a phaeochromocytoma (PH) approached that of the controls (C) at low and higher concentrations of unlabeled insulin. The apparent receptor affinity was unchanged (ED50: PH 0.50×10−9M and C0.60×10−9M). Scatchard analysis of the binding data using the negative cooperative model revealed a 46% decrease in the total number of receptors together with no changes in both K−e (PH 0.55×109M−1 and C 0.36×109M−1) and K−f (PH 0.13×109 M−1 and C 0.07×109 M−1). According to the two site model, an altered proportion in the two classes of insulin binding sites was detected. This was accompanied by a catecholamine-desensitization of the adipocytes to the antilipolytic action of insulin. These events could represent a final situation of a chronic and endogeneous regulation by high levels of catecholamines of insulin receptors in human adipose tissue.

scholarly journals Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

2007 ◽  
Vol 51 (8) ◽  
pp. 1397-1403 ◽  
Author(s):  
Daniela Espíndola-Antunes ◽  
Claudio E. Kater
Keyword(s):  
Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Human Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Cushing's Syndrome ◽  
Intact Cells ◽  
Fat Depots ◽  
Cortisol Metabolism ◽  
The Metabolic Syndrome

Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a NADPH-dependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11betaHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11betaHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11betaHSD1 also in human adipose tissue. However, 11betaHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11betaHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11betaHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11betaHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.

Subclinical Cushing’s Syndrome in women with adrenal incidentalomas is associated with adipose tissue dysfunction

2016 ◽  
Vol 62 (5) ◽  
pp. 72-73
Author(s):  
Stavroula A. Paschou ◽  
Markella Nezi ◽  
Fotini Dimitropoulou ◽  
Dimitrios Ioannidis ◽  
Argyro Panagiotakou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Visceral Adiposity Index ◽  
Adrenal Incidentalomas ◽  
Subclinical Cushing’S Syndrome ◽  
Adipose Tissue Dysfunction ◽  
Mass Size ◽  
And Function

Introduction. The visceral adiposity index (VAI) is a mathematical formula based on simple anthropometric and biochemical parameters and reflects the distribution and function of the adipose tissue.Aim: to investigate the possible association between the presence of subclinical Cushing’s syndrome (SCS) and VAI in patients with adrenal incidentalomas.Patients and methods. We studied 258 patients with adrenal incidentalomas. The diagnosis of SCS was based on a post-LDDST cortisol level ≥1.8 mg/dl combined with an abnormal result of at least one other test of the HPA axis, in the absence of clinical signs. The VAI index was calculated as following: Women VAI= [WC/36.58+(1.89×BMI)] ×(TG/0.81)×(1.52/HDL), Men VAI= [WC/39.68+(1.88×BMI)] ×(TG/1.03)×(1.31/HDL).Results. 122 patients were excluded from the analysis due to overt metabolic problems (8 with BMI>39, 82 with metabolic syndrome and 34 with type 2 diabetes). Among 136 patients who were included in the analysis (42M/94W, 56.9±9.7 y), SCS was diagnosed in 24 (17.6%). Patients with SCS presented with significantly higher levels of insulin (12.4±4.6 vs 9.9±3.2 μIU/ml, p=0.036) and triglycerides (114±36 vs 97±34 mg/dl, p=0.023), larger size of tumors (3.26±0.88 vs 2.28±1.06 cm, p<0.001) and higher calculated VAI (1.77±0.83 vs 1.39±0.69, p=0.045). Regression analysis revealed that the presence of SCS was positively associated with VAI [OR (95% CI) 1.888 (1.051–3.394), p=0.034] but when gender subgroup analysis followed, this was shown only in women [OR (95% CI) 2.284 (1.135–4.595), p=0.021]. Another important prognostic factor for the probability of SCS was the mass size [OR (95% CI) 2.237 (1.441–3.472), p<0.001].Conclusion. SCS in women with adrenal incidentalomas is associated with adipose tissue dysfunction.

scholarly journals Changes in Adenosine 5′-Monophosphate-Activated Protein Kinase as a Mechanism of Visceral Obesity in Cushing’s Syndrome

2008 ◽  
Vol 93 (12) ◽  
pp. 4969-4973 ◽  
Author(s):  
Blerina Kola ◽  
Mirjam Christ-Crain ◽  
Francesca Lolli ◽  
Giorgio Arnaldi ◽  
Gilberta Giacchetti ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Abdominal Surgery ◽  
Visceral Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Central Obesity ◽  
Cushing's Syndrome ◽  
Metabolic Effects ◽  
Ampk Activity ◽  
Visceral Adipose

Objective: Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing’s syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing’s syndrome. Methods: AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing’s syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. Results: The patients with Cushing’s syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P &lt; 0.001, respectively). Downstream targets of AMPK fatty acid synthase and phosphoenol-pyruvate carboxykinase were up-regulated in patients with Cushing’s syndrome. AMPK activity was inversely correlated with 0900 h serum cortisol and with urinary free cortisol. Conclusions: Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing’s syndrome.

scholarly journals Adipose tissue 11β-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing’s syndrome

2006 ◽  
Vol 155 (3) ◽  
pp. 435-441 ◽  
Author(s):  
Barbara Mariniello ◽  
Vanessa Ronconi ◽  
Silvia Rilli ◽  
Paolo Bernante ◽  
Marco Boscaro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Western Blot ◽  
Cushing’S Syndrome ◽  
Blot Analysis ◽  
Plasma Cortisol ◽  
Cushing's Syndrome ◽  
Normal Weight ◽  
Omental Adipose Tissue ◽  
Obese Subjects

Objective: To evaluate the expression of 11β-hydrxysteroid dehydrogenase type 1 (11β-HSD1) in omental adipose tissue of patients with Cushing’s syndrome and simple obesity, compared with normal weight controls. Design and methods: We have performed a case-control study and studied omental adipose tissue from a total of 24 subjects (eight obese subjects, ten patients with Cushing’s syndrome due to adrenal adenoma, and six normal weight controls). Body mass index, blood pressure, plasma glucose, plasma insulin, plasma cortisol, urinary free cortisol and post dexamethasone plasma cortisol were measured with standard methods. 11β-HSD1 mRNA and protein expression were evaluated in real-time PCR and western blot analysis respectively. Results: 11β-HSD1 mRNA was 13-fold higher in obese subjects compared with controls (P=0.001). No differences were found between Cushing’s patients and controls. Western blot analysis supported the mRNA expression results. Conclusions: Our data show the involvement of 11β-HSD1 enzyme invisceral obesity, which is more evident in severely obese patients than in Cushing’s syndrome patients. The lack of increase of 11β-HSD1 expression in Cushing’s syndrome could suggest downregulation of the enzyme as a result of long-term overstimulation.

Long Term Effect of Noradrenaline on Insulin Binding to Human Adipose Tissue “In Vitro”

1986 ◽  
Vol 18 (10) ◽  
pp. 718-719 ◽  
Author(s):  
M. Cigolini ◽  
C. Zancanaro ◽  
E. Cavallo ◽  
D. Benati ◽  
S. Ferrari ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Insulin Binding ◽  
Term Effect ◽  
Adipose Tissue In Vitro ◽  
Long Term Effect

scholarly journals Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate

1989 ◽  
Vol 258 (1) ◽  
pp. 147-155 ◽  
Author(s):  
F Montiel ◽  
J Ortiz-Caro ◽  
A Villa ◽  
A Pascual ◽  
A Aranda
Keyword(s):  
Fatty Acids ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Scatchard Analysis ◽  
Maximal Effect ◽  
C6 Cells ◽  
Receptor Affinity ◽  
Chain Fatty Acids

The presence of insulin receptor and its regulation by butyrate and other short-chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells.

scholarly journals Comparison of adipose tissue derived genes in endogenous Cushing’s syndrome versus diet-induced obesity

2019 ◽  
Vol 70 (2) ◽  
pp. 131-134
Author(s):  
Judit Denes ◽  
Adrienn Zsippai ◽  
Laszlo Kovacs ◽  
Zoltan Gorombey ◽  
Gabor L. Kovacs ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Diet Induced Obesity
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