The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients.

Abstract:

AIMS/HYPOTHESIS:Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion. Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes. METHODS:Pancreatic samples and/or isolated islets from non-diabetic controls (ND) and type 2 diabetes patients were evaluated for insulin secretion, apoptosis (electron microscopy and ELISA), morphometric ER assessment (electron microscopy), and expression of ER stress markers in beta cell prepared by laser capture microdissection and in isolated islets. RESULTS:Insulin release was lower and beta cell apoptosis higher in type 2 diabetes than ND islets. ER density volume was significantly increased in type 2 diabetes beta cells. Expression of alpha-mannosidase (also known as mannosidase, alpha, class 1A, member 1) and UDP-glucose glycoprotein glucosyl transferase like 2 (UGCGL2), assessed by microarray and/or real-time reverse transcriptase polymerase chain reaction (RT-PCR), differed between ND and type 2 diabetes beta cells. Expression of immunoglobulin heavy chain binding protein (BiP, also known as heat shock 70 kDa protein 5 [glucose-regulated protein, 78 kDa] [HSPA5]), X-box binding protein 1 (XBP-1, also known as XBP1) and C/EBP homologous protein (CHOP, also known as damage-inducible transcript 3 [DDIT3]) was not higher in type 2 diabetes beta cell or isolated islets cultured at 5.5 mmol/l glucose (microarray and real-time RT-PCR) than in ND samples. When islets were cultured for 24 h at 11.1 mmol/l glucose, there was induction of BiP and XBP-1 in type 2 diabetes islets but not in ND islets. CONCLUSIONS/INTERPRETATION:Beta cell in type 2 diabetes showed modest signs of ER stress when studied in pancreatic samples or isolated islets maintained at physiological glucose concentration. However, exposure to increased glucose levels induced ER stress markers in type 2 diabetes islet cells, which therefore may be more susceptible to ER stress induced by metabolic perturbations.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Marchetti P,Bugliani M,Lupi R,Marselli L,Masini M,Boggi U,Filipponi F,Weir GC,Eizirik DL,Cnop M

doi

10.1007/s00125-007-0816-8

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

2486-94

issue

12

eissn

0012-186X

issn

1432-0428

journal_volume

50

pub_type

杂志文章
  • Beta-cell cytoplasmic Ca2+ balance as a determinant for glucose-stimulated insulin release.

    abstract::The introduction of new techniques and the access to clonal lines of insulin-secreting cells have enabled re-evaluation of glucose effects on Ca2+ movements in pancreatic beta cells. It became evident that glucose, in addition to stimulating the entry of Ca2+, also promotes active sequestration of the ion in intracell...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00281983

    authors: Hellman B

    更新日期:1985-08-01 00:00:00

  • Use of class I and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations.

    abstract:AIMS/HYPOTHESIS:The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes. METHODS:Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the T...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-012-2608-z

    authors: Valdes AM,Erlich HA,Carlson J,Varney M,Moonsamy PV,Noble JA

    更新日期:2012-09-01 00:00:00

  • Impaired glucose tolerance (IGT) is associated with reduced insulin-induced suppression of glucagon concentrations.

    abstract:AIMS/HYPOTHESIS:We aimed to examine whether impaired glucose tolerance is associated with reduced suppression of glucagon concentrations. METHODS:Eighty-four non-diabetic women of Caucasian origin and 61 years of age, of whom 48 had normal glucose tolerance (NGT) and 36 had IGT, underwent a 75 g OGTT and a hyperinsuli...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250100003

    authors: Ahrén B,Larsson H

    更新日期:2001-11-01 00:00:00

  • Lack of insulin receptors affects the formation of white adipose tissue in mice. A morphometric and ultrastructural analysis.

    abstract::Lack of insulin receptors in mice is associated with near-normal intrauterine growth, unlike patients with leprechaunism, in whom growth deficiency is a prominent clinical feature. Genetic crosses of insulin receptor- and insulin-like growth-factor-1 (IGF-1) receptor-deficient mice indicate, however, that insulin rece...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050886

    authors: Cinti S,Eberbach S,Castellucci M,Accili D

    更新日期:1998-02-01 00:00:00

  • Growth hormone effect on accumulation of arterial basement membrane-like material studied on rabbit aortic myomedial cell cultures.

    abstract::The effect of human growth hormone on arterial basement membrane-like (BM) material was studied. BM-like material was obtained from the cell layer of cultured aortic myomedial cells using a sonication-differential centrifugation technique. After the addition of small amounts of growth hormone (1 ng/ml) to the cultures...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00703138

    authors: Ledet T,Heickendorff L

    更新日期:1985-12-01 00:00:00

  • Imprecision of new criteria for the oral glucose tolerance test.

    abstract::Subjects selected from a centre specializing in diabetes detection have been classified using nine different methods of diagnosis including the recent criteria of the National Diabetes Data Group and the World Health Organization. The applicability of these two new criteria have been evaluated and compared with seven ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00297390

    authors: Massari V,Eschwège E,Valleron AJ

    更新日期:1983-02-01 00:00:00

  • Acute and chronic effects of troglitazone (CS-045) on isolated rat ventricular cardiomyocytes.

    abstract::Freshly isolated and primary cultured adult rat cardiomyocytes were used to elucidate the mechanism of action of the new oral antidiabetic agent (+/-)-5-[4-(6-hydroxy-2, 5, 7, 8-tetramethyl-chroman-2-yl-methoxy)benzyl]-2,4-thiazolidinedione (troglitazone) on the heart. Interaction with protein kinase C (PKC) and regul...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050509

    authors: Bähr M,Spelleken M,Bock M,von Holtey M,Kiehn R,Eckel J

    更新日期:1996-07-01 00:00:00

  • Abnormal regulation of sympathetic nervous activity and heart rate after oral glucose in type 1 (insulin-dependent) diabetic patients.

    abstract::Oral glucose administration increased plasma noradrenaline concentration significantly in seven normal subjects (p less than 0.02), whereas in six young short-term Type 1 diabetic patients without complications plasma noradrenaline did not change. Basal plasma noradrenaline did not differ between the two groups. In th...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00279937

    authors: Hegedüs L,Christensen NJ,Sestoft L

    更新日期:1983-09-01 00:00:00

  • Gene expression profiling of diabetic and galactosaemic cataractous rat lens by microarray analysis.

    abstract:AIMS/HYPOTHESIS:Osmotic and oxidative stress is associated with the progression and advancement of diabetic cataract. In the present study, we used a cDNA microarray method to analyse gene expression patterns in streptozotocin-induced diabetic rats and galactose-fed cataractous lenses. In addition, we investigated the ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1687-5

    authors: Kubo E,Singh DP,Akagi Y

    更新日期:2005-04-01 00:00:00

  • Functional studies in patients with the glucagonoma syndrome.

    abstract::Four patients with glucagon-producing tumours of the pancreas were investigated. Fasting plasma glucagon concentrations ranged from 209--625 pmol/l. Plasma insulin concentrations were normal except in one patient, where the tumour also produced insulin (558 pmol/l). Intravenous glucose (25 g/m2) depressed the glucagon...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF01219741

    authors: Holst JJ,Helland S,Ingemannson S,Pedersen NB,von Schenck H

    更新日期:1979-09-01 00:00:00

  • Effect of acute hyperglycaemia on plasma potassium and aldosterone levels in type 2 (non-insulin-dependent) diabetes.

    abstract::Potassium homeostasis during a 50-g oral glucose tolerance test was studied in 14 newly diagnosed, untreated Type 2 (non-insulin-dependent) diabetics. They showed a rise in plasma potassium from a mean +/- SEM basal of 3.9 +/- 0.1 to 4.4 +/- 0.1 mmol/l at 60 min and to 4.6 +/- 0.1 mmol/l at 90 min (p less than 0.01), ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00283750

    authors: Rosenstock J,Loizou SA,Brajkovich IE,Mashiter K,Joplin GF

    更新日期:1982-03-01 00:00:00

  • The diabesity epidemic in the light of evolution: insights from the capacity-load model.

    abstract::The global nutrition transition, which embraces major changes in how food is produced, distributed and consumed, is associated with rapid increases in the prevalence of obesity, but the implications for diabetes differ between populations. A simple conceptual model treats diabetes risk as the function of two interacti...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-019-4944-8

    authors: Wells JCK

    更新日期:2019-10-01 00:00:00

  • Dysregulation of glucose transport in hearts of genetically obese (fa/fa) rats.

    abstract::Overall D-glucose metabolism and 3-0-methylglucose transport were measured in the perfused heart preparation of lean and genetically obese (fa/fa) rats. Absolute values of basal and insulin-stimulated glucose metabolism were decreased in hearts of 15-week-old obese rats when compared to lean age-matched controls. Basa...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00284464

    authors: Zaninetti D,Crettaz M,Jeanrenaud B

    更新日期:1983-12-01 00:00:00

  • Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.

    abstract:AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. METHODS:In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing allele...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-014-3308-7

    authors: Zhu J,Zong G,Lu L,Gan W,Ji L,Hu R,Ye X,Sun L,Loos RJ,Li H,Lin X

    更新日期:2014-09-01 00:00:00

  • Cardiovascular and alcohol-related deaths in abnormal glucose tolerant and diabetic subjects.

    abstract::The aim of this study was to compare the causes of death and parameters related to alcohol consumption, between subjects diagnosed as diabetic, clinically by their general practitioner, or glucose intolerant and in particular as diabetic, using the epidemiological criteria of an abnormal glucose level following an ora...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00400850

    authors: Balkau B,Eschwège E,Fontbonne A,Claude JR,Warnet JM

    更新日期:1992-01-01 00:00:00

  • Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:Insulin-like growth factor-1 is a major childhood growth factor and promotes pancreatic islet cell survival and growth in vitro. We hypothesised that genetic variation in IGF1 might be associated with childhood growth, glucose metabolism and type 1 diabetes risk. We therefore examined the association be...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-0970-7

    authors: Vella A,Bouatia-Naji N,Heude B,Cooper JD,Lowe CE,Petry C,Ring SM,Dunger DB,Todd JA,Ong KK

    更新日期:2008-05-01 00:00:00

  • Human mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 diabetic patients.

    abstract:AIMS/HYPOTHESIS:Mesenchymal stem cells (MSCs) can exert an immunosuppressive effect on any component of the immune system, including dendritic cells (DCs), by direct contact, the release of soluble markers and extracellular vesicles (EVs). We evaluated whether MSCs and MSC-derived EVs have an immunomodulatory effect on...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-015-3808-0

    authors: Favaro E,Carpanetto A,Caorsi C,Giovarelli M,Angelini C,Cavallo-Perin P,Tetta C,Camussi G,Zanone MM

    更新日期:2016-02-01 00:00:00

  • The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes.

    abstract:AIMS/HYPOTHESIS:Recent genome-wide association studies have suggested that a polymorphism in GCKR, the gene encoding the glucokinase regulatory protein, is involved in triacylglycerol regulation. Our aim was to examine in large-scale studies the common GCKR rs780094 polymorphism in relation to metabolic traits (mainly ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-007-0865-z

    authors: Sparsø T,Andersen G,Nielsen T,Burgdorf KS,Gjesing AP,Nielsen AL,Albrechtsen A,Rasmussen SS,Jørgensen T,Borch-Johnsen K,Sandbaek A,Lauritzen T,Madsbad S,Hansen T,Pedersen O

    更新日期:2008-01-01 00:00:00

  • Sulfate metabolism in the alloxan-diabetic rat: relationship of altered sulfate pools to proteoglycan sulfation in heart and other tissues.

    abstract::The incorporation of [35S]sulfate into heart proteoglycans has been studied in normal and alloxan-diabetic rats by perfusion and in vivo administration of the isotope; in the latter situation, comparison was also made of radiolabeled sulfate utilization by several other tissues (kidney, liver, lung, muscle, testes and...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00270425

    authors: Spiro MJ

    更新日期:1987-04-01 00:00:00

  • Neuronal control of peripheral nutrient partitioning.

    abstract::The appropriate utilisation, storage and conversion of nutrients in peripheral tissues, referred to as nutrient partitioning, is a fundamental process to adapt to nutritional and metabolic challenges and is thus critical for the maintenance of a healthy energy balance. Alterations in this process during nutrient exces...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-020-05104-9

    authors: Manceau R,Majeur D,Alquier T

    更新日期:2020-04-01 00:00:00

  • Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

    abstract:AIMS/HYPOTHESIS:In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. METHODS:Wom...

    journal_title:Diabetologia

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00125-014-3344-3

    authors: d'Emden MC,Jenkins AJ,Li L,Zannino D,Mann KP,Best JD,Stuckey BG,Park K,Saltevo J,Keech AC,FIELD Study Investigators.

    更新日期:2014-11-01 00:00:00

  • G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1.

    abstract:AIMS/HYPOTHESIS:Activation of the G protein-coupled receptor (GPR)40 by long-chain fatty acids potentiates glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells, and GPR40 agonists are in clinical development for type 2 diabetes therapy. GPR40 couples to the G protein subunit Gα(q/11) but the signallin...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-012-2650-x

    authors: Ferdaoussi M,Bergeron V,Zarrouki B,Kolic J,Cantley J,Fielitz J,Olson EN,Prentki M,Biden T,MacDonald PE,Poitout V

    更新日期:2012-10-01 00:00:00

  • Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study.

    abstract:AIMS/HYPOTHESIS:We aimed to examine the effects of bariatric surgery on microvascular complications in patients with type 2 diabetes using objective measures. METHODS:Prospective case-control study of 70 obese surgical patients with type 2 diabetes undergoing gastric bypass surgery matched for age, sex and duration of...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-015-3595-7

    authors: Miras AD,Chuah LL,Khalil N,Nicotra A,Vusirikala A,Baqai N,Graham C,Ravindra S,Lascaratos G,Oliver N,le Roux CW

    更新日期:2015-07-01 00:00:00

  • How does glucose regulate the human pancreatic A cell in vivo?

    abstract::To investigate the mechanism whereby changes in plasma glucose level alter human pancreatic A-cell activity in vivo, A-cell activity was determined during manipulation of plasma glucose and pancreatic B-cell activity by insulin and glucose infusions. A-cell activity (the acute immunoreactive glucagon response to intra...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00252408

    authors: Asplin CM,Hollander PM,Palmer JP

    更新日期:1984-03-01 00:00:00

  • Mast cells and type VIII collagen in human diabetic nephropathy.

    abstract::Renal injury in diabetes mellitus is associated with progressive interstitial fibrosis and extracellular matrix accumulation. However, the phenotypes of cells forming the interstitial infiltrate in diabetic nephropathy have not been precisely defined. There is increasing evidence for the association of mast cells with...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF02658509

    authors: Rüger BM,Hasan Q,Greenhill NS,Davis PF,Dunbar PR,Neale TJ

    更新日期:1996-10-01 00:00:00

  • Fluorescence of oxidized flavoproteins from perifused isolated pancreatic islets.

    abstract::In perifused pancreatic islets, the fluorescence of oxidized flavoproteins (FAD) was recorded continuously. Elevation of glucose concentration in the medium form 0 or 5 mM to 20 mM led to decrease in FAD-fluorescence beginning 10 sec after change of medium. L-leucine (10 mM), (+/-)-B-BCH (20 mM) and alpha-ketoisocapro...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF01222108

    authors: Panten U,Ishida H

    更新日期:1975-12-01 00:00:00

  • IRS1 degradation and increased serine phosphorylation cannot predict the degree of metabolic insulin resistance induced by oxidative stress.

    abstract:AIM/HYPOTHESIS:Oxidative stress was shown to selectively induce impaired metabolic response to insulin, raising the possible involvement of alterations in Insulin-Receptor-Substrate (IRS) proteins. This study was conducted to assess whether oxidative stress induced IRS protein degradation and enhanced serine phosphoryl...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-003-1097-5

    authors: Potashnik R,Bloch-Damti A,Bashan N,Rudich A

    更新日期:2003-05-01 00:00:00

  • Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids.

    abstract:AIMS/HYPOTHESIS:Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect o...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0369-2

    authors: Hoeks J,Hesselink MK,Russell AP,Mensink M,Saris WH,Mensink RP,Schrauwen P

    更新日期:2006-10-01 00:00:00

  • Increased energy expenditure in poorly controlled Type 1 (insulin-dependent) diabetic patients.

    abstract::The basal energy expenditure of 10 Type 1 (insulin-dependent) C-peptide-negative diabetic patients (2042 +/- 62 kcal/24 h) was found to be significantly higher than the 1774 +/- 52 kcal/24 h predicted from their age, sex and body surface area (p less than 0.01). Intravenous insulin treatment significantly reduced ener...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00253494

    authors: Nair KS,Halliday D,Garrow JS

    更新日期:1984-07-01 00:00:00

  • A radioreceptor-assay for glucagon: binding of enteroglucagon to liver plasma membranes.

    abstract::A radioreceptor-assay for glucagon was developed employing pig liver plasma membranes isolated by means of an aqueous two-phase polymer system. The assay is simple, precise, and has a detection limit of 40 pg/ml. Acid-ethanol extracts of porcine intestinal mucosa and entero-glucagon purified by affinity chromatography...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00422324

    authors: Holst JJ

    更新日期:1975-06-01 00:00:00