Abstract:
OBJECTIVE:Adrenaline inhibits insulin secretion through activation of alpha(2)-adrenoceptors (ARs). These receptors are linked to pertussis toxin-sensitive G proteins. Agonist binding leads to inhibition of adenylyl cyclase, inhibition of Ca(2+) channels and activation of K(+) channels. Recently, three distinct subtypes of alpha(2)-AR were described, alpha(2A)-AR, alpha(2B)-AR and alpha(2C)-AR. At present, it is unknown which of these alpha(2)-AR subtype(s) may regulate insulin secretion. We used mice deficient in alpha(2)-ARs to analyze the coupling and role of individual alpha(2)-AR subtypes in insulin-secreting beta cells. METHODS:The inhibitory effect of adrenaline on insulin secretion was measured in freshly isolated and cultured wild type (wt) and alpha(2)-AR knockout (KO) mouse islets in order to examine the receptor subtypes which mediate adrenaline-induced inhibition of insulin secretion. Adenylyl cyclase activity was measured in isolated cultured islets. Membrane potential was measured using the amphotericin B permeabilized patch clamp method in isolated and cultured single islet cells. RESULTS:In wt, alpha(2A)- and alpha(2C)-AR KO mouse islets, adrenaline, 1 microM/L, inhibited secretion by 83, 80 and 100% respectively. In contrast, in alpha(2A/2C)-AR double KO mouse islets, adrenaline had no effect on stimulated secretion indicating that both alpha(2A)-AR and alpha(2C)-AR, but not alpha(2B)-AR, are functionally expressed in mouse islets. Surprisingly, glucose (16.7 mM/L)-induced secretion in the presence of 1 microM/L forskolin was greatly impaired in alpha(2A)-AR KO islets. However, when cAMP levels were increased further by the combination of forskolin (5 microM/L) and 3-isobutyl-1-methylxanthine (100 microM/L), secretion was stimulated 2.7-fold (8.5-fold in wt islets). Adrenaline lowered the concentration of cAMP in wt and alpha(2C)-AR KO mouse islets by 74%. Adrenaline also hyperpolarized wt and alpha(2C)-AR KO beta cells. In contrast, adrenaline did not inhibit adenylyl cyclase in islets of alpha(2A)-AR KO mice, nor did it hyperpolarize alpha(2A)-AR KO beta cells. CONCLUSION:Adrenaline inhibits insulin release through alpha(2A)- and alpha(2C)-ARs via distinct intracellular signaling pathways.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Peterhoff M,Sieg A,Brede M,Chao CM,Hein L,Ullrich Sdoi
10.1530/eje.0.1490343subject
Has Abstractpub_date
2003-10-01 00:00:00pages
343-50issue
4eissn
0804-4643issn
1479-683Xjournal_volume
149pub_type
杂志文章abstract:OBJECTIVE:The aim of the study was to evaluate the effect of intraoperative high-field (1.5 Tesla) magnetic resonance imaging (MRI) on the results of transsphenoidal surgery of GH-secreting pituitary macroadenomas. METHODS:Twenty-three acromegalic patients (mean tumor size, 25 +/- 12 mm; untreated preoperative GH, 4.2...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.1.01970
更新日期:2005-08-01 00:00:00
abstract:INTRODUCTION:The fetus is most vulnerable to severe iodine deficiency and hypothyroidism during pregnancy. The effects of mild iodine deficiency and subclinical hypothyroidism are poorly known. The present study assesses the association between thyroid hormones (TH)s and urinary iodine concentration (UIC) in healthy pr...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-08-0716
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testo...
journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/eje.1.02126
更新日期:2006-04-01 00:00:00
abstract::Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first describ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330166
更新日期:1995-08-01 00:00:00
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journal_title:European journal of endocrinology
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更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE:To identify predictors of the PEGV dose requ...
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pub_type: 杂志文章
doi:10.1530/EJE-16-0956
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVES:The aim of the present study was to determine vascular endothelial growth factor (VEGF), prostaglandin E(2) (PGE(2)) and active renin levels in patients with hormonally active adrenal tumours. DESIGN:The study was comprised of 16 patients with primary aldosteronism, 13 patients with active Cushing's syndrom...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1500345
更新日期:2004-03-01 00:00:00
abstract::The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330527
更新日期:1995-11-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1430285
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Lithium, clinically used in the treatment of bipolar disorders, is well known to induce thyroid growth. However, the mechanism involved is only incompletely characterized. Although it is conventionally believed that thyroid proliferation depends on the thyroid-stimulating hormone (TSH)/cAMP/cAMP response ele...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02038
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:To determine if human growth hormone (hGH) replacement therapy alters pharmacokinetics of hydrocortisone (CS) substitution in hypopituitary adults. DESIGN:To this aim, we analysed serum and salivary CS profiles 270 min after oral CS administration at baseline and 6 and 12 months after initiation of hGH repla...
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pub_type: 杂志文章
doi:10.1530/eje.0.1430769
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVE:Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed. DESIGN:Prospective investigation. METHODS:Ninety-five women with PCOS were ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0398
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:The antagonism of Agouti protein (AP) and Agouti-related protein on melanocortin receptors suggests an inhibitory role in the regulation of steroidogenesis. However, we have previously demonstrated that ectopic AP overexpression increased restraint-induced corticosterone release and adrenal reactivity to ACTH...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1510613
更新日期:2004-11-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0043
更新日期:2009-08-01 00:00:00
abstract::To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditi...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380076
更新日期:1998-01-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0532
更新日期:2008-03-01 00:00:00
abstract::Thyroid-stimulating hormone (TSH), like the other pituitary glycoprotein hormones, is produced and secreted as a mixture of isoforms, the majority of which represent differences in oligosaccharide structure and possess different bioactivity. When samples are quantified simultaneously by immunometric assay and bioassay...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.1310331
更新日期:1994-10-01 00:00:00
abstract::Several cytokines have been shown to be expressed in normal and adenomatous pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We have investigated further the presence of IL-8 mRNA, using in situ hybridisation in...
journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:1999-02-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
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更新日期:2019-07-01 00:00:00
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更新日期:2003-03-01 00:00:00
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更新日期:2007-06-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1410035
更新日期:1999-07-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
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更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Individuals carrying a heterozygous inactivating PAX8 mutation are affected by congenital hypothyroidism (CH), although heterozygous Pax8 knockout mice are not. It has remained unclear whether CH in PAX8 mutation carriers is caused by haploinsufficiency or a dominant negative mechanism. OBJECTIVE:To report ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0410
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:Mutations in HESX1 represent a rare cause of GH deficiency (GHD) associated with a broad spectrum of other anomalies. We searched for causative mutations in a cohort of 244 Italian patients affected by combined and isolated GHD (IGHD). METHODS:The HESX1 gene-coding region and exon-intron boundaries were scre...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0047
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVE:Inactivating mutations of the GH-releasing hormone receptor (GHRHR) gene (GHRHR) cause familial isolated GH deficiency (IGHD) type IB. The GH response to physical exercise (PE) in patients lacking GHRHR has never been studied. We hypothesized that subjects lacking functional GHRHR may be a model to study GH r...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1470591
更新日期:2002-11-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:The molecular mechanisms of TSH receptor (TSHR) activation and intramolecular signal transduction are largely unknown. Deletion of the extracellular domain (ECD) of the TSHR results in increased constitutive activity, which suggests a self-inhibitory interaction between the ECD and the extracellular loops (EC...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.01891
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND:Sleep behavior is changing toward shorter sleep duration and a later chronotype. It results in a sleep debt that is acquitted on work-free days, inducing a small but recurrent sleep misalignment each week, referred to as "social jetlag". These sleep habits could affect health through misalignment with circad...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0188
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:For patients who remain hypothyroid despite the administration of what would seem adequate doses of levothyroxine (L-T4), the underlying cause can be difficult to determine. The possibility of a biological cause should first be explored; however, in the majority of cases, poor adherence to medication is likel...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-1035
更新日期:2013-05-10 00:00:00