IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice.


AIMS/HYPOTHESIS:Aggregation of islet amyloid polypeptide (IAPP) to form amyloid contributes to beta cell dysfunction in type 2 diabetes. Human but not non-amyloidogenic rodent IAPP induces islet macrophage proIL-1β synthesis. We evaluated the effect of IL-1 receptor antagonist (IL-1Ra) on islet inflammation and dysfunction in a mouse model of type 2 diabetes with amyloid formation. METHODS:Lean and obese male mice (A/a or A(vy)/A at the agouti locus, respectively) with or without beta cell human IAPP expression (hIAPP(Tg/0)) were treated with PBS or IL-1Ra (50 mg kg(-1) day(-1)) from 16 weeks of age. Intraperitoneal glucose and insulin tolerance tests were performed after 8 weeks. Pancreases were harvested for histology and gene expression analysis. RESULTS:Aggregation of human IAPP was associated with marked upregulation of proinflammatory gene expression in islets of obese hIAPP(Tg/0) mice, together with amyloid deposition and fasting hyperglycaemia. IL-1Ra improved glucose tolerance and reduced plasma proinsulin:insulin in both lean and obese hIAPP(Tg/0) mice with no effect on insulin sensitivity. The severity and prevalence of islet amyloid was reduced by IL-1Ra in lean hIAPP (Tg/0) mice, suggesting a feed-forward mechanism by which islet inflammation promotes islet amyloid at the early stages of disease. IL-1Ra limited Il1a, Il1b, Tnf and Ccl2 expression in islets from obese hIAPP(Tg/0) mice, suggesting an altered islet inflammatory milieu. CONCLUSIONS/INTERPRETATION:These data provide the first in vivo evidence—using a transgenic mouse model with amyloid deposits resembling those found in human islets—that IAPP-induced beta cell dysfunction in type 2 diabetes may be mediated by IL-1. Anti-IL-1 therapies may limit islet inflammation and dysfunction associated with amyloid formation.






Westwell-Roper CY,Chehroudi CA,Denroche HC,Courtade JA,Ehses JA,Verchere CB




Has Abstract


2015-03-01 00:00:00












  • Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion.

    abstract:AIMS/HYPOTHESIS:We investigated the association of variants of the transcription factor 7-like 2 (TCF7L2) gene with: (1) incident diabetes in the Finnish Diabetes Prevention Study (DPS, Study I); (2) type 2 diabetes and impaired glucose regulation (i.e. IGT or IFG) in a cross-sectional study (Study II); and (3) insulin...


    pub_type: 杂志文章


    authors: Wang J,Kuusisto J,Vänttinen M,Kuulasmaa T,Lindström J,Tuomilehto J,Uusitupa M,Laakso M

    更新日期:2007-06-01 00:00:00

  • Screening blood glucose values: effects of season and time of day.

    abstract::Blood glucose screening results, obtained using two different screening procedures, are reported from two occupational groups. Post-prandial blood glucose levels were measured in 3346 subjects aged 45 years or more employed by the Greater London Council/Inner London Education Authority. In women, mean blood glucose le...


    pub_type: 杂志文章


    authors: Jarrett RJ,Murrells TJ,Shipley MJ,Hall T

    更新日期:1984-12-01 00:00:00

  • N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.

    abstract:AIMS/HYPOTHESIS:The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet-monocyte conjugation in blood from patients with type 2 diabetes. METHODS:In this placebo-controlled randomised crossover stu...


    pub_type: 杂志文章,随机对照试验


    authors: Treweeke AT,Winterburn TJ,Mackenzie I,Barrett F,Barr C,Rushworth GF,Dransfield I,MacRury SM,Megson IL

    更新日期:2012-11-01 00:00:00

  • Glucose tolerance and other determinants of cardiovascular autonomic function: the Hoorn Study.

    abstract:AIMS/HYPOTHESIS:Currently, three categories of measures are used to assess cardiovascular autonomic dysfunction: measures of the Ewing-test, measures of heart-rate variability, and measures of baroreflex sensitivity. We studied the determinants of these measures obtained from cardiovascular autonomic function tests in ...


    pub_type: 杂志文章


    authors: Gerritsen J,Dekker JM,TenVoorde BJ,Bertelsmann FW,Kostense PJ,Stehouwer CD,Heine RJ,Nijpels G,Heethaar RM,Bouter LM

    更新日期:2000-05-01 00:00:00

  • The effect of improvement in diabetic control on plasma and whole blood viscosity.

    abstract::Rheological studies were made on the blood of 12 diabetic patients after a period of poor diabetic control (HbA1 12.6 +/- 0.7% (mean +/- SD); mean home capillary blood glucose level 11.7 +/- 1.2 mmol/l), and after at least three months of improved control (HbA1 9.1 +/- 0.4%, p < 0.01; mean home capillary blood glucose...


    pub_type: 杂志文章


    authors: Paisey RB,Harkness J,Hartog M,Chadwick T

    更新日期:1980-10-01 00:00:00

  • Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.

    abstract::The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after re...


    pub_type: 杂志文章


    authors: Mingrone G,DeGaetano A,Greco AV,Capristo E,Benedetti G,Castagneto M,Gasbarrini G

    更新日期:1997-05-01 00:00:00

  • Microvascular permeability to albumin and glomerular filtration rate in diabetic and normal children.

    abstract::In order to examine the permeability of microvessels in diabetic children, the glomerular filtration rate, urinary excretion rates of albumin and beta 2-microglobulin, intravascular mass of albumin, and transcapillary escape rate of albumin were studied in 26 diabetic children without clinical signs of microangiopathy...


    pub_type: 杂志文章


    authors: Brøchner-Mortensen J,Ditzel J,Mogensen CE,Rødbro P

    更新日期:1979-05-01 00:00:00

  • Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine.

    abstract::The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased in...


    pub_type: 杂志文章


    authors: Madsen KL,Ariano D,Fedorak RN

    更新日期:1995-04-01 00:00:00

  • Height and glucose tolerance in adult subjects.

    abstract::In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentratio...


    pub_type: 杂志文章


    authors: Brown DC,Byrne CD,Clark PM,Cox BD,Day NE,Hales CN,Shackleton JR,Wang TW,Williams DR

    更新日期:1991-07-01 00:00:00

  • Determination of peritoneal glucose kinetics in rats: implications for the peritoneal implantation of closed-loop insulin delivery systems.

    abstract::Peritoneal glucose kinetics were evaluated in the anaesthetized rat, to assess whether the peritoneal cavity would be a suitable site for the implantation of membrane-protected islets of Langerhans (bioartificial pancreas) or the glucose sensor of an artificial B cell. Glucose was measured in peritoneal fluid samples ...


    pub_type: 杂志文章


    authors: Velho G,Froguel P,Reach G

    更新日期:1989-06-01 00:00:00

  • A genetic marker at the glucokinase gene locus for type 2 (non-insulin-dependent) diabetes mellitus in Mauritian Creoles.

    abstract::The prevalence of Type 2 (non-insulin-dependent) diabetes mellitus is high in Mauritius, a multiethnic island nation in the southwestern Indian Ocean. Evaluation of candidate genes in the different ethnic groups represents a means of assessing the genetic component. As glucokinase is known to be a key regulator of glu...


    pub_type: 杂志文章


    authors: Chiu KC,Province MA,Dowse GK,Zimmet PZ,Wagner G,Serjeantson S,Permutt MA

    更新日期:1992-07-01 00:00:00

  • Ins1(Cre) knock-in mice for beta cell-specific gene recombination.

    abstract:AIMS/HYPOTHESIS:Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy of m...


    pub_type: 杂志文章


    authors: Thorens B,Tarussio D,Maestro MA,Rovira M,Heikkilä E,Ferrer J

    更新日期:2015-03-01 00:00:00

  • Stimulation of adipose tissue lipolysis following insulin-induced hypoglycaemia: evidence of increased beta-adrenoceptor-mediated lipolytic response in IDDM.

    abstract::The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 con...


    pub_type: 杂志文章


    authors: Bolinder J,Sjöberg S,Arner P

    更新日期:1996-07-01 00:00:00

  • Inhibition of matrix-induced bone differentiation by advanced glycation end-products in rats.

    abstract::Glycation of long-lived proteins is an inevitable consequence of aging that is accelerated in patients with diabetes mellitus. Treatment of demineralized bone matrix particles from 35-week-old normal Long-Evans rats with glycoaldehyde, a precursor of advanced glycation end-products, was used to assess the effects of b...


    pub_type: 杂志文章


    authors: Fong Y,Edelstein D,Wang EA,Brownlee M

    更新日期:1993-09-01 00:00:00

  • Hypoxia and hypoxia-inducible factors in diabetes and its complications.

    abstract::Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues are hypoxic but adaptive responses to hypoxia are impaired due to insufficient activation of HIF signalling, which results from inhibition of HIF-1α stability and function due to hypergly...


    pub_type: 杂志文章,评审


    authors: Catrina SB,Zheng X

    更新日期:2021-01-26 00:00:00

  • Diabetes as a risk factor for stroke. A population perspective.

    abstract::Stroke incidence, case fatality and mortality in diabetic patients were compared to non-diabetic subjects in a 35-74-year-old population in northern Sweden (target population 241,000). During an 8-year period, 1,544 stroke events in diabetic patients and 4,826 events in non-diabetic subjects were recorded. The crude i...


    pub_type: 杂志文章


    authors: Stegmayr B,Asplund K

    更新日期:1995-09-01 00:00:00

  • Insulin action and determinants of glycaemia in a rat model of type 2 (non-insulin-dependent) diabetes mellitus.

    abstract::We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (non-insulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the g...


    pub_type: 杂志文章


    authors: Pascoe WS,Jenkins AB,Kusunoki M,Storlien LH

    更新日期:1992-03-01 00:00:00

  • Birthweight and early-onset type 2 diabetes in American Indians: differential effects in adolescents and young adults and additive effects of genotype, BMI and maternal diabetes.

    abstract:AIMS/HYPOTHESIS:The aim of this work was to estimate the impact of birthweight on early-onset (age <40 years) type 2 diabetes. METHODS:A longitudinal study of American Indians, aged ≥5 years, was conducted from 1965 to 2007. Participants who had a recorded birthweight were followed until they developed diabetes or the...


    pub_type: 杂志文章


    authors: Olaiya MT,Wedekind LE,Hanson RL,Sinha M,Kobes S,Nelson RG,Baier LJ,Knowler WC

    更新日期:2019-09-01 00:00:00

  • The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence Finnish and the medium-incidence Hungarian populations.

    abstract:AIMS/HYPOTHESIS:The rs1990760 polymorphism (Ala946Thr) of interferon induced with helicase C domain 1 (IFIH1) has been proposed to associate with type 1 diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes was investigated in two distinct white populations, the Hungarians and Finns. METHODS...


    pub_type: 杂志文章


    authors: Jermendy A,Szatmári I,Laine AP,Lukács K,Horváth KH,Körner A,Madácsy L,Veijola R,Simell O,Knip M,Ilonen J,Hermann R,Finnish Paediatric Diabetes Registry.,HUNT1DGENES Programme.

    更新日期:2010-01-01 00:00:00

  • Absence of telomere shortening and oxidative DNA damage in the young adult offspring of women with pre-gestational type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:The offspring of mothers with pre-gestational type 1 diabetes (PGDM) may be at increased risk of glucose intolerance and cardiovascular disease in childhood. The underlying causes of these observations, and whether they persist into adulthood, are unknown. The aim of the present study was to test the hy...


    pub_type: 杂志文章


    authors: Cross JA,Brennan C,Gray T,Temple RC,Dozio N,Hughes JC,Levell NJ,Murphy H,Fowler D,Hughes DA,Sampson MJ

    更新日期:2009-02-01 00:00:00

  • The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass.

    abstract:AIMS/HYPOTHESIS:The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. METHODS:A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which ...


    pub_type: 杂志文章


    authors: Bobbioni-Harsch E,Sztajzel J,Barthassat V,Lehmann TN,Sievert K,Chassot G,Huber O,Morel P,Golay A,Assimacopoulos-Jeannet F

    更新日期:2005-07-01 00:00:00

  • Cost-utility analyses of intensive blood glucose and tight blood pressure control in type 2 diabetes (UKPDS 72).

    abstract:AIMS/HYPOTHESIS:This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight. METHODS:We conducted cost-utility analysis based...


    pub_type: 杂志文章


    authors: Clarke PM,Gray AM,Briggs A,Stevens RJ,Matthews DR,Holman RR,UKPDS 72 United Kingdom Prospective Diabetes Study.

    更新日期:2005-05-01 00:00:00

  • Engineered cell lines for insulin replacement in diabetes: current status and future prospects.

    abstract::The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas transplantation over the past three decades, the broad-scale appl...


    pub_type: 杂志文章,评审


    authors: Newgard CB,Clark S,BeltrandelRio H,Hohmeier HE,Quaade C,Normington K

    更新日期:1997-07-01 00:00:00

  • Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats.

    abstract:AIMS/HYPOTHESIS:The glomerular endothelial layer is coated by the endothelial surface layer (ESL), which is suggested to play a role in regulation of the permselectivity of macromolecules. Production of heparanase, a degrading enzyme of the ESL, is induced by reactive oxygen species (ROS). We hypothesised that oxidativ...


    pub_type: 杂志文章


    authors: Kuwabara A,Satoh M,Tomita N,Sasaki T,Kashihara N

    更新日期:2010-09-01 00:00:00

  • Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane.

    abstract::In diabetic nephropathy, expression of glycosaminoglycan side chains of heparan sulphate proteoglycan in the glomerular basement membrane is reduced proportionally to the degree of proteinuria. We performed a cross-sectional study to evaluate whether non-vascular basement membranes also show a decrease in heparan sulp...


    pub_type: 杂志文章


    authors: van der Pijl JW,Daha MR,van den Born J,Verhagen NA,Lemkes HH,Bucala R,Berden JH,Zwinderman AH,Bruijn JA,van Es LA,van der Woude FJ

    更新日期:1998-07-01 00:00:00

  • Direct effect of GLP-1 infusion on endogenous glucose production in humans.

    abstract:AIMS/HYPOTHESIS:Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusio...


    pub_type: 临床试验,杂志文章


    authors: Seghieri M,Rebelos E,Gastaldelli A,Astiarraga BD,Casolaro A,Barsotti E,Pocai A,Nauck M,Muscelli E,Ferrannini E

    更新日期:2013-01-01 00:00:00

  • Spousal cardiometabolic risk factors and incidence of type 2 diabetes: a prospective analysis from the English Longitudinal Study of Ageing.

    abstract:AIMS/HYPOTHESIS:In the UK, more than one million people have undiagnosed diabetes and an additional five million are at high risk of developing the disease. Given that early identification of these people is key for both primary and secondary prevention, new screening approaches are needed. Since spouses resemble each ...


    pub_type: 杂志文章


    authors: Nielsen J,Hulman A,Witte DR

    更新日期:2018-07-01 00:00:00

  • Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids.

    abstract:AIMS/HYPOTHESIS:According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as i...


    pub_type: 杂志文章,多中心研究


    authors: Rump P,Popp-Snijders C,Heine RJ,Hornstra G

    更新日期:2002-03-01 00:00:00

  • Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients.

    abstract:AIMS/HYPOTHESIS:Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes. METHODS:Liver biopsy samples were obtaine...


    pub_type: 杂志文章


    authors: Takamura T,Sakurai M,Ota T,Ando H,Honda M,Kaneko S

    更新日期:2004-04-01 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...


    pub_type: 杂志文章


    authors: Zaninetti D,Crettaz M,Jeanrenaud B

    更新日期:1983-12-01 00:00:00