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Wang, Minghan

doi:10.1186/1743-7075-2-3

Cited by 234 publications

(85 citation statements)

References 191 publications

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“…This has been proposed to underlie the effects of low-protein diet on offspring phenotypes such as development of hypertension [20,23]. Glucocorticoid excess has been linked to clinical observations associated with the metabolic syndrome such as central obesity, hypertension, hyperlipidaemia and glucose intolerance [27]. These clinical features associated with glucocorticoids are similar to the phenotypic traits that are programmed in utero following feeding of LP diets in rat pregnancy [9,18].…”

Section: Discussionmentioning

confidence: 94%

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

Erhuma¹,

McMullen²,

Langley‐Evans³

et al. 2009

Endocr

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Prenatal exposure to a low-protein diet programmes altered expression of genes that regulate lipid metabolism, including SREBP-1c. The main aim of this study was to investigate whether programmed changes to hepatic SREBP-1c expression in the rat are glucocorticoid-dependent. Rats were fed isocaloric diets (control or low-protein) throughout pregnancy. The low-protein group received 11beta-hydroxylase inhibitor, the inhibitor plus corticosterone, or vehicle injections over the first 2 weeks of pregnancy. The control group was administered vehicle injections only. On delivery the animals were transferred to a standard chow diet. The offspring were weaned at 4 weeks of age on to the same chow diet and killed for collection of liver tissue. The inhibitor of glucocorticoid synthesis reversed the suppressive effect of low-protein diet on hepatic SREBP-1c expression of both protein and mRNA seen in low-protein exposed offspring. To test if this effect is through direct effect on the SREBP-1c promoter, H4IIE cells were transfected with a luciferase reporter construct controlled by the SREBP-1c promoter treated with dexamethasone. Dexamethasone induced the expression of SREBP-1c in vitro. Together these studies demonstrate that foetal over-exposure to glucocorticoids, through indirect mechanism, play a crucial role in low-protein-diet-induced changes in lipid metabolism regulating genes.

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Section: Discussionmentioning

confidence: 94%

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

Erhuma¹,

McMullen²,

Langley‐Evans³

et al. 2009

Endocr

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“…This fact is relevant, taking into account that we studied strictly controlled normoweight neonates. It has been suggested that insulin resistance accompanied by hypercortisolaemia may be important in the development of metabolic syndrome in adults [34].…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance markers in term, normoweight neonates. The Mérida cohort

Gesteiro¹,

Bastida

Sánchez‐Muniz

2008

Eur J Pediatr

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Several endocrine regulators are implicated in the development of metabolic syndrome. The aim of our study was to assess normal ranges for glucose, growth hormone (GH), insulin-like growth factor-1 (IGF-1), cortisol, insulin and the yet-to-be-published quantitative insulin sensitivity check index (QUICKI) for newborns and a number of homeostatic model assessment (HOMA)-related equations that have been proposed as indicators of insulin sensitivity (HOMA-S) and insulin resistance (HOMA-R). The study included 115 (54 males, 61 females) singleton, normoweight, Spanish Caucasian neonates delivered without foetal distress from mothers of the Mérida (Spain) Birth Cohort who tested negative in the O'Sullivan screen. Neonatal normal values given as the mean (95% confidence interval) were: glucose, 75.3 mg/dL (68.29-82.29); cortisol, 7.4 microg/dL (6.85-7.97); GH, 16.7 ng/mL (14.87-18.60); insulin, 5.5 microUI/mL (4.12-6.88), IGF-155.2 ng/mL (50.82-59.53); QUICKI, 0.45 (0.43-0.48); HOMA-R, 1.36 (0.84-1.88); HOMA-S, 4.07 (2.66-5.49), the glucose/insulin ratio, 33.6 (24.58-42.67); the insulin/cortisol ratio, 0.8 (0.61-1.05). Hormone ranges (except for cortisol, whose values were lower) were equivalent to those of other studies. Cortisolaemia values cannot be associated with the type of delivery, as only three births (2.6%) were by caesarean section, while 20 (17.4%) were instrumental deliveries. Neonates from the lowest quartile of the insulin/cortisol ratio presented higher (p < 0.001) HOMA-S and QUICKI and lower (p < 0.01) HOMA-R values. The results of our study indicate normal ranges for insulin resistance and sensitivity at birth. The insulin/cortisol ratio at birth appears to be a good early indicator of insulin resistance.

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“…[2][3][4][5] Numerous studies have implicated glucocorticoid action in the regulation of hepatic gluconeogenesis and lipogenesis, glucose uptake and lipid oxidation in skeletal muscle, and the production of angiotensinogen. [6][7][8] Patients with Cushing's syndrome have increased glucocorticoid exposure and exhibit similar symptoms compared with those with metabolic syndrome, including insulin resistance, high adiposity, dyslipidemia and hypertension. [9] These metabolic abnormities in Cushing's syndrome could be improved to a certain degree by decreasing the excessive glucocorticoid action through surgery or glucocorticoid receptor antagonist treatment.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors

Pradaux-Caggiano

Thomas

et al. 2010

ChemMedChem

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11Beta-hydroxysteroid dehydrogenases (11beta-HSDs) are key enzymes regulating the pre-receptor metabolism of glucocorticoid hormones. The modulation of 11beta-HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue-specific glucocorticoid action by regulating 11beta-HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11beta-HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11beta-HSD1 with IC(50) values in the 50-70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X-ray crystal structures of human 11beta-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.

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Cited by 234 publications

References 191 publications

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism

Insulin resistance markers in term, normoweight neonates. The Mérida cohort

Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors

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