Ectopic expression of neurogenin 3 in neonatal pig pancreatic precursor cells induces (trans)differentiation to functional alpha cells.


AIMS/HYPOTHESIS:Neurogenin 3 (NEUROG3), a basic helix-loop-helix transcription factor that is needed for endocrine cell development in the embryonic pancreas, has been shown to induce transdifferentiation of duct cells from adult pancreas towards a neuro-endocrine phenotype. Our study explored the endocrine transdifferentiation potential of NEUROG3 in neonatal pancreatic precursor cells. MATERIALS AND METHODS:A replication-deficient adenovirus expressing Neurog3 and green fluorescent protein (GFP) (Ad-NEUROG3) was used to infect neonatal pig pancreatic cell preparations enriched for endocrine islet and cytokeratin-positive precursor cells. GFP-positive cells were sorted using flow cytometry on days 3 and 8 after infection and characterised at the transcript and protein level. For in vivo experiments, the total population of Ad-NEUROG3-infected pancreatic cells was transplanted, then later removed for determination of graft hormone content and immunohistochemistry. RESULTS:Among the GFP-positive cells, the fraction of precursor cells decreased by more than 85% at day 8 after infection, while the fraction of glucagon-positive cells increased 2.5-fold and the beta cell number remained the same. Transplantation of the Ad-NEUROG3-infected pancreatic cell preparation failed to reverse streptozotocin-induced hyperglycaemia, while non-infected cells and a control cell preparation infected with replication-deficient adenovirus expressing only GFP were able to do so. At day 109 after transplantation, kidneys grafted with Ad-NEUROG3-infected pancreatic cells contained significantly decreased insulin and increased glucagon levels. Abundant glucagon-immunopositive cells were seen in Ad-NEUROG3-infected grafts, which were virtually devoid of proliferating insulin-positive cells. CONCLUSIONS/INTERPRETATION:In summary, adenoviral delivery of NEUROG3 to pancreatic precursor cells from neonatal pig pancreas promotes alpha cell differentiation in vitro and in vivo.






Harb G,Heremans Y,Heimberg H,Korbutt GS




Has Abstract


2006-08-01 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

  • Autoantibodies to nervous tissue structures are associated with autonomic neuropathy in type 1 (insulin-dependent) diabetes mellitus.

    abstract::There is evidence that the immune system may play a role in the pathogenesis of autonomic neuropathy in Type 1 (insulin-dependent) diabetes mellitus. In the present study, we investigated the presence of autoantibodies to sympathetic and parasympathetic nervous structures and their correlation with other conventional ...


    pub_type: 杂志文章


    authors: Zanone MM,Peakman M,Purewal T,Watkins PJ,Vergani D

    更新日期:1993-06-01 00:00:00

  • Pairing-up SOX to kick-start beta cell genesis.

    abstract::The transcription factor SOX9 is regarded as a crucial player in pancreas development, both maintaining progenitors and later being required for beta cell differentiation. However, very little is known about the possible involvement of other SOX family members in such processes. In this issue, the work of Xu et al (DO...


    pub_type: 评论,杂志文章


    authors: Grapin-Botton A,Seymour PA,Gradwohl G

    更新日期:2015-05-01 00:00:00

  • Intra-axonal recording from large sensory myelinated axons: demonstration of impaired membrane conductances in early experimental diabetes.

    abstract:AIM/HYPOTHESIS:Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not w...


    pub_type: 杂志文章


    authors: Kriz J,Padjen AL

    更新日期:2003-02-01 00:00:00

  • Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora's box.

    abstract::Over a century ago, inquisitive physicians made remarkable discoveries regarding pancreatic pathology in individuals with diabetes, including those who were likely afflicted with the type 1 (autoimmune) form of the disease. Those studies of post-mortem tissues noted unique anatomical changes in islet architecture as w...


    pub_type: 评论,杂志文章


    authors: Atkinson MA

    更新日期:2014-04-01 00:00:00

  • Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease.

    abstract:AIMS/HYPOTHESIS:Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant chemokin...


    pub_type: 杂志文章


    authors: Nicoletti F,Conget I,Di Mauro M,Di Marco R,Mazzarino MC,Bendtzen K,Messina A,Gomis R

    更新日期:2002-08-01 00:00:00

  • The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens.

    abstract:AIMS/HYPOTHESIS:Enterovirus infections are among the environmental risk factors potentially contributing to the pathogenesis of Type 1 diabetes. The aim of this study was to evaluate virus-host interaction by analysing the enterovirus antibody levels in subjects carrying different HLA-DR alleles associated with either ...


    pub_type: 杂志文章


    authors: Sadeharju K,Knip M,Hiltunen M,Akerblom HK,Hyöty H

    更新日期:2003-08-01 00:00:00

  • Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome.

    abstract::In a population-based survey of 2,930 subjects, prevalence rates for obesity, Type 2 (non-insulin-dependent) diabetes mellitus, impaired glucose tolerance, hypertension, hypertriglyceridaemia, and hypercholesterolaemia were 54.3, 9.3, 11.1, 9.8, 10.3 and 9.2%, respectively. The prevalence, however, of each of these co...


    pub_type: 杂志文章


    authors: Ferrannini E,Haffner SM,Mitchell BD,Stern MP

    更新日期:1991-06-01 00:00:00

  • Familial risk of type I diabetes in European children. The Eurodiab Ace Study Group and The Eurodiab Ace Substudy 2 Study Group.

    abstract::The characteristics of familial Type I (insulin-dependent) diabetes mellitus-that is Type I diabetes in a first degree relative were investigated for children diagnosed before the age of 15 years using data from an international network of population-based registries (the EURODIAB ACE network) and from a case-control ...


    pub_type: 杂志文章



    更新日期:1998-10-01 00:00:00

  • Abnormal islet sphingolipid metabolism in type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes ...


    pub_type: 杂志文章


    authors: Holm LJ,Krogvold L,Hasselby JP,Kaur S,Claessens LA,Russell MA,Mathews CE,Hanssen KF,Morgan NG,Koeleman BPC,Roep BO,Gerling IC,Pociot F,Dahl-Jørgensen K,Buschard K

    更新日期:2018-07-01 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...


    pub_type: 杂志文章


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

    更新日期:1998-02-01 00:00:00

  • cAMP response element binding protein H mediates fenofibrate-induced suppression of hepatic lipogenesis.

    abstract:AIMS/HYPOTHESIS:Fenofibrate is a drug used to treat hyperlipidaemia that works by inhibiting hepatic triacylglycerol synthesis. Sterol regulatory element binding protein-1c (SREBP-1c) is a major regulator of the expression of genes involved in hepatic triacylglycerol synthesis. In addition, endoplasmic reticulum (ER)-b...


    pub_type: 杂志文章


    authors: Min AK,Jeong JY,Go Y,Choi YK,Kim YD,Lee IK,Park KG

    更新日期:2013-02-01 00:00:00

  • Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study.

    abstract::To evaluate the behaviour and predictive value of islet cell and insulin autoantibodies in patients with organ-specific autoimmune diseases, we followed 21 non-diabetic subjects for a mean period of 84 +/- 27 months. Ten patients were persistently seropositive for complement-fixing islet cell antibodies and high titre...


    pub_type: 杂志文章


    authors: Betterle C,Presotto F,Pedini B,Moro L,Slack RS,Zanette F,Zanchetta R

    更新日期:1987-05-01 00:00:00

  • No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort.

    abstract:AIMS/HYPOTHESIS:Although the variable number tandem repeat (VNTR) minisatellite 5' to the insulin gene is among the most studied polymorphisms in diabetes, the relationships between VNTR variation, diabetes-related traits and predisposition to type 2 diabetes remain unclear. Since inadequate sample size is likely to ha...


    pub_type: 杂志文章,多中心研究


    authors: Bennett A,Sovio U,Ruokonen A,Martikainen H,Pouta A,Taponen S,Hartikainen AL,Franks S,Peltonen L,Elliott P,Järvelin MR,McCarthy MI

    更新日期:2005-05-01 00:00:00

  • Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes.

    abstract:AIMS/HYPOTHESIS:IRS2 is an important molecular switch that mediates insulin signalling in the liver. IRS2 dysregulation is responsible for the phenomenon of selective insulin resistance that is observed in type 2 diabetes. We hypothesise that epigenetic mechanisms are involved in the regulation of IRS2 in the liver of ...


    pub_type: 杂志文章


    authors: Krause C,Geißler C,Tackenberg H,El Gammal AT,Wolter S,Spranger J,Mann O,Lehnert H,Kirchner H

    更新日期:2020-10-01 00:00:00

  • Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus.

    abstract::The antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences were found between diabetic pat...


    pub_type: 杂志文章


    authors: Diepersloot RJ,Bouter KP,Beyer WE,Hoekstra JB,Masurel N

    更新日期:1987-06-01 00:00:00

  • Differential relationship between physical activity and progression to diabetes by glucose tolerance status: the Inter99 Study.

    abstract:AIMS/HYPOTHESIS:The aim of the study was to analyse how strongly commuting and leisure-time physical activity affect progression to diabetes and to study whether this relationship is different in individuals with isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT). METHODS:We stud...


    pub_type: 杂志文章


    authors: Engberg S,Glümer C,Witte DR,Jørgensen T,Borch-Johnsen K

    更新日期:2010-01-01 00:00:00

  • Glucose regulates both glucose transport and the glucose transporter gene expression in a hamster-derived pancreatic beta-cell line (HIT).

    abstract::We studied the effect of chronic exposure to high glucose on the glucose transport regulation in hamster pancreatic Beta cells in permanent culture (HIT). Cells were exposed to either 5.5 mmol/l or 16.7 mmol/l glucose for 48 h and then glucose transport was studied by measuring the (3H)-2-deoxyglucose uptake for 5 and...


    pub_type: 杂志文章


    authors: Purrello F,Buscema M,Vetri M,Vinci C,Gatta C,Forte F,Rabuazzo AM,Vigneri R

    更新日期:1991-05-01 00:00:00

  • Prognostic impact of the ankle-brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

    abstract:AIMS/HYPOTHESIS:The prognostic importance of the ankle-brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes. METHODS:The ABI was measured at baseline in ...


    pub_type: 杂志文章


    authors: Cardoso CRL,Melo JV,Salles GC,Leite NC,Salles GF

    更新日期:2018-11-01 00:00:00

  • Down regulation of peroxisome proliferator-activated receptorgamma expression by inflammatory cytokines and its reversal by thiazolidinediones.

    abstract:AIMS/HYPOTHESIS:Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptory (PPARgamma). We hypothesized that the anti-diabetic mechanism of thia...


    pub_type: 杂志文章


    authors: Tanaka T,Itoh H,Doi K,Fukunaga Y,Hosoda K,Shintani M,Yamashita J,Chun TH,Inoue M,Masatsugu K,Sawada N,Saito T,Inoue G,Nishimura H,Yoshimasa Y,Nakao K

    更新日期:1999-06-01 00:00:00

  • Abnormal distribution of VLDL subfractions in type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role?

    abstract::Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate thes...


    pub_type: 杂志文章


    authors: Patti L,Romano G,Di Marino L,Annuzzi G,Mancini M,Riccardi G,Rivellese AA

    更新日期:1993-02-01 00:00:00

  • Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in c...


    pub_type: 杂志文章


    authors: Feng AL,Xiang YY,Gui L,Kaltsidis G,Feng Q,Lu WY

    更新日期:2017-06-01 00:00:00

  • Islet cell autoimmunity and mitochondrial DNA mutation in Korean subjects with typical and atypical Type I diabetes.

    abstract:AIMS/HYPOTHESIS:The 1997 American Diabetes Association classification of diabetes mellitus included a subset of Type I diabetic patients who do not need insulin for several years but eventually progress to complete insulin deficiency i. e. atypical Type I diabetes mellitus. In Caucasian populations, most Type I diabeti...


    pub_type: 杂志文章


    authors: Lee WJ,Lee HW,Palmer JP,Park KS,Lee HK,Park JY,Hong SK,Lee KU

    更新日期:2001-12-01 00:00:00

  • Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake.

    abstract:AIMS/HYPOTHESIS:In early type 1 diabetes mellitus, renal salt handling is dysregulated, so that the glomerular filtration rate becomes inversely proportional to salt intake. The salt paradox occurs in both humans and rats and, with low salt intake, results in diabetic hyperfiltration. We tested whether increased salt i...


    pub_type: 杂志文章


    authors: Sima CA,Koeners MP,Joles JA,Braam B,Magil AB,Cupples WA

    更新日期:2012-08-01 00:00:00

  • Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand.

    abstract:AIMS/HYPOTHESIS:Our aims were to compare osteoclastic activity between patients with acute Charcot's osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). METHODS:Peripheral blood m...


    pub_type: 杂志文章


    authors: Mabilleau G,Petrova NL,Edmonds ME,Sabokbar A

    更新日期:2008-06-01 00:00:00

  • Protein kinase C isoforms beta 1 and beta 2 inhibit the tyrosine kinase activity of the insulin receptor.

    abstract::Downregulation of insulin receptor tyrosine kinase (IRK) activity yields to impaired insulin signalling and contributes to the pathogenesis of cellular insulin resistance. Activation of protein kinase C (PKC) by different agents is associated with an inhibition of IRK activity in various cell types. There is evidence ...


    pub_type: 杂志文章


    authors: Bossenmaier B,Mosthaf L,Mischak H,Ullrich A,Häring HU

    更新日期:1997-07-01 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...


    pub_type: 杂志文章


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

    更新日期:1992-01-01 00:00:00

  • Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999-2000). Groupe de Recherche Rhin Rhĵne Alpes Genève pour la transplantation d'Ilots de Langerhans.

    abstract:AIMS/HYPOTHESIS:Improvements in islet transplantation require clinical series large enough to implement controlled new strategies. The goal of this study was to demonstrate the feasibility of a multicentre network for islet transplantation in Type I (insulin-dependent) diabetic patients. METHODS:The five centres (Besa...


    pub_type: 杂志文章,多中心研究


    authors: Benhamou PY,Oberholzer J,Toso C,Kessler L,Penfornis A,Bayle F,Thivolet C,Martin X,Ris F,Badet L,Colin C,Morel P,GRAGIL consortium.

    更新日期:2001-07-01 00:00:00

  • A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria.

    abstract:AIMS/HYPOTHESIS:Patients with glucokinase mutations are characterised by mild, persistent fasting hyperglycaemia, a small increment in glucose in response to an oral load and a dominant family history. These patients frequently present with gestational diabetes and often require insulin treatment during pregnancy. We a...


    pub_type: 杂志文章


    authors: Ellard S,Beards F,Allen LI,Shepherd M,Ballantyne E,Harvey R,Hattersley AT

    更新日期:2000-02-01 00:00:00

  • Insulin-induced activation of phosphoinositide 3-kinase in Fao cells.

    abstract::Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85 alph...


    pub_type: 杂志文章


    authors: Hayashi T,Okamoto M,Yoshimasa Y,Inoue G,Yamada K,Kono S,Shigemoto M,Suga J,Kuzuya H,Nakao K

    更新日期:1996-05-01 00:00:00