Abstract:
Aim:To establish pancreatic alpha-cell mass in lean, non-diabetic humans over the adult lifespan, performed as a follow-up study to beta-cell mass across the adult human lifespan. Methods:We examined human pancreatic autopsy tissue from 66 lean, non-diabetic individuals aged from 30 to 102 years, grouped into deciles: 3rd (30-39 years), 4th (40-49 years), 5th (50-59 years), 6th (60-69 years), 7th (70-79 years), 8th (80-89 years) and 9th deciles (90+ years). Sections of pancreas were immunostained for glucagon and analyzed for fractional alpha-cell area. Population-based pancreatic volume data were used to calculate alpha-cell mass. Results:With advanced age, the exocrine pancreas undergoes atrophy demonstrated by increased fat area (as % exocrine area) (0.05 ± 0.01 vs 1.6 ± 0.7% fat area of total exocrine pancreas, 3rd vs 9th decile, P < 0.05). Consequently, islet density increases with age (2.7 ± 0.4 vs 10.5 ± 3.3 islets/mm2, 3rd vs 9th decile, P < 0.05). Alpha-cell fractional area increases with advanced age (0.34 ± 0.05% vs 0.73 ± 0.26%, 3rd vs 9th decile, P < 0.05). However, alpha-cell mass remains constant at ~190 mg throughout the adult lifespan in lean, non-diabetic humans. Within islets, alpha-cell distribution between mantle and core is unchanged across deciles (1862 ± 220 vs 1945 ± 200 vs 1948 ± 139 alpha cells in islet mantle/mm2, 3rd vs 6th vs 9th decile, P = 0.93 and 1912 ± 442 vs 1449 ± 123 vs 1514 ± 168 alpha cells in islet core/mm2, 3rd vs 6th vs 9th decile, P = 0.47), suggesting that human islets retain their structural organization in the setting of age-related exocrine atrophy. Conclusions:Consistent with our previous findings for beta-cell mass, alpha-cell mass remains constant in humans, even with advanced age. Pancreatic endocrine cells are much more robustly preserved than exocrine cells in aged humans, and islets maintain their structural integrity throughout life.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Moin ASM,Cory M,Gurlo T,Saisho Y,Rizza RA,Butler PC,Butler AEdoi
10.1530/EJE-19-0844subject
Has Abstractpub_date
2020-02-01 00:00:00pages
219-231issue
2eissn
0804-4643issn
1479-683Xpii
EJE-19-0844.R2journal_volume
182pub_type
杂志文章abstract:OBJECTIVE:Excess glucocorticoids are known to cause hypertension and cardiovascular disease (CVD). The BclI glucocorticoid receptor (GR) polymorphism increases glucocorticoid sensitivity and is associated with adverse metabolic effects. Previous studies investigating cardiovascular implications have shown inconsistent ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-15-0381
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Elevated levels of circulating fibroblast growth factor 21 (FGF21) are commonly encountered in type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, all of which share exaggerated postprandial lipemia as a common proatherogenic feature. How FGF21 responds to an oral fat load in man is unknown...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0783
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:Paraoxonase-1 (PON-1), which has PON and arylesterase activities, is a high-density lipoprotein (HDL)-bound antioxidant enzyme that inhibits atherosclerosis. Diabetes has been shown to have an impact on oxidative stress. The effect of metabolic syndrome (MetS) on oxidative stress and PON-1 has been shown befo...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0732
更新日期:2010-03-01 00:00:00
abstract:Context:The human adrenal is the dominant source of androgens in castration-resistant prostate cancer (CRPC) and classic 21-hydroxylase deficiency (21OHD). Abiraterone, derived from the prodrug abiraterone acetate (AA), inhibits the activity of cytochrome P450 17-hydroxylase/17,20-lyase (CYP17A1), the enzyme required f...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0905
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVE:Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of i...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1530/EJE-11-1061
更新日期:2012-04-01 00:00:00
abstract::The secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is regulated by gonadotropin-releasing hormone (GnRH). As men age, mean serum concentrations of immunoreactive gonadotropic hormones tend to increase, while serum testosterone concentrations tend to decline. To evaluate age-related change...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1530/eje.0.1350399
更新日期:1996-10-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of Rosiglitazone in three patients treated with bilateral adrenalectomy followed by hyperpigmentation and hypersecretion of ACTH. PATIENTS AND METHODS:One patient had increasing ACTH after previous transsphenoidal surgery for Nelson's syndrome, and two patients without pituitary ade...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.01994
更新日期:2005-10-01 00:00:00
abstract::Pituitary tumours express both somatostatin and dopamine receptors. Medical treatment with somatostatin analogues is a cornerstone of GH- and TSH-secreting tumours, while treatment with dopamine agonists is a cornerstone of prolactin-secreting tumours. Dopamine agonists have also demonstrated some efficacy in patients...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.1.02348
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:X-linked adrenoleukodystrophy (X-ALD) is the most frequent, severely neurodegenerative, clinically heterogeneous peroxisomal disorder, the signs of which are a consequence of myelin, adrenal cortex, and testes impairment. OBJECTIVE:We studied testosterone, LH, and FSH levels in X-ALD/adrenomyeloneuropathy (...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0490
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:Validate the acromegaly quality of life (AcroQoL) questionnaire as a disease-generated questionnaire, which analyses physical and psychological domains, the latter subdivided into appearance and personal relationship sub-scales, to evaluate health-related quality of life (HRQoL) in acromegaly. DESIGN:Prospec...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/eje.1.02214
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:To study whether serum parathyroid hormone (PTH) and serum calcium are associated with body mass index (BMI), and their predicting role in obesity. DESIGN:Population based, cross-sectional study. METHODS:In 2001 a population-based health survey was held in Tromsø, North Norway. Questionnaires on medical his...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1510167
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:To evaluate the impact of long-term, non-suppressive levothyroxine (L-T(4)) treatment on quantitative ultrasonometry in women. DESIGN:This was a case-control study. SUBJECTS AND METHODS:Altogether 667 women (mean age+/-s.d., 49.5+/-13.1 years) were studied. Of these, 156 (23%) had non-toxic goitre or hypoth...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1420445
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:The association of hyperparathyroidism (HPT) with thyroid disease has long been known, but the mechanisms underlying such an association have not yet been clarified. OBJECTIVE:To elucidate the main factors determining this combination of endocrine diseases, in a retrospective multicenter study. METHODS:We ...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/eje.0.1450429
更新日期:2001-10-01 00:00:00
abstract::Design Hypercortisolism during pregnancy is a risk factor for prematurity. Long-term exposure to hypercortisolism may lead to permanent comorbidities, such as hypertension or diabetes, even after remission. Our aim was to determine whether women with a history of Cushing's disease (and being eu-, hypo- or hypercortiso...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-20-1224
更新日期:2021-01-01 00:00:00
abstract:Background/objective:Data on metabolic impairments in Cushing's syndrome and GH deficiency all suggest that the relationship between cortisol and GH/IGF-I axis in obesity may have a role in the related diseases. However, studies focusing only on one of these hormones are often controversial in paediatrics. We aimed to ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0792
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:Several factors either predisposing or protecting from the onset of diabetes mellitus type 2 (DM2) have been proposed. Two specific polymorphisms of toll-like receptor 4 (TLR4; Asp299Gly and Thr399Ile) have recently been identified either as candidate protector genes against DM2 and associated neuropathy or r...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0280
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:In Cushing's disease (CD), GH responsiveness to several stimuli, including ghrelin, GHRP-6, and GHRH, is blunted. Recovery of GH secretion after remission of hypercortisolism after transsphenoidal surgery, radiotherapy, or adrenalectomy is controversial. There are no studies evaluating the effect of primary c...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0459
更新日期:2009-11-01 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
abstract:DESIGN:In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal childre...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0042
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:The relationship between sex hormones and hepatocellular adenoma development is well established. On the contrary, their contribution to liver adenomatosis (LA) development is still a debatable issue. Recently, inactivating mutations of hepatocyte nuclear factor-1alpha (HNF-1alpha) transcription factor gene o...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0020
更新日期:2007-06-01 00:00:00
abstract::The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents. It is unclear at pre...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380501
更新日期:1998-05-01 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:The existence of genotype-phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations. DESIGN AND METHODS:Study cohort included 8...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0195
更新日期:2007-09-01 00:00:00
abstract:OBJECTIVE:To compare baseline characteristics in adult patients with growth hormone (GH) deficiency (GHD) who had previously been treated for Cushing's disease or acromegaly with data from patients with GHD of other aetiologies. To study the effects of GH therapy in those patients who had completed at least 6 months of...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1460067
更新日期:2002-01-01 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
doi:10.1530/eje.0.1400155
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
doi:10.1530/EJE-09-0043
更新日期:2009-08-01 00:00:00
abstract:OBJECTIVE:Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on beta-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to ...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1530/eje.0.1510039
更新日期:2004-07-01 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...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0956
更新日期:2017-04-01 00:00:00
abstract:Objective:Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease. Design and methods:Pati...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1530/EJE-19-0159
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVE:In the last decade, surgery of primary hyperparathyroidism (HPT) due to a solitary adenoma has moved on from the traditional wide bilateral neck exploration (BNE) to more limited approaches such as unilateral neck exploration and minimally invasive parathyroidectomy. DESIGN:To define the role of intraoperati...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1490007
更新日期:2003-07-01 00:00:00