Artifactual insulin release from differentiated embryonic stem cells.


:Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.






Hansson M,Tonning A,Frandsen U,Petri A,Rajagopal J,Englund MC,Heller RS,Håkansson J,Fleckner J,Sköld HN,Melton D,Semb H,Serup P




Has Abstract


2004-10-01 00:00:00
















  • Gliotransmission and brain glucose sensing: critical role of endozepines.

    abstract::Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process. Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secret...


    pub_type: 杂志文章


    authors: Lanfray D,Arthaud S,Ouellet J,Compère V,Do Rego JL,Leprince J,Lefranc B,Castel H,Bouchard C,Monge-Roffarello B,Richard D,Pelletier G,Vaudry H,Tonon MC,Morin F

    更新日期:2013-03-01 00:00:00

  • Insulin-dependent childhood diabetes. Normal viability of cultured fibroblasts.

    abstract::Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inhere...


    pub_type: 杂志文章


    authors: Rosenbloom AL,Rosenbloom EK

    更新日期:1978-03-01 00:00:00

  • Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is glucose dependent: implications for long-term regulation of lipolysis.

    abstract::Tumor necrosis factor-alpha (TNF-alpha) and hyperglycemia both impair insulin sensitivity in vivo. This may be secondary to stimulation of adipose tissue lipolysis and consequent increased circulating free fatty acids (FFAs). Here we report that neither TNF-alpha nor glucose alone has a pronounced effect on lipolysis ...


    pub_type: 杂志文章


    authors: Green A,Rumberger JM,Stuart CA,Ruhoff MS

    更新日期:2004-01-01 00:00:00

  • Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients.

    abstract::Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE recept...


    pub_type: 杂志文章


    authors: Poirier O,Nicaud V,Vionnet N,Raoux S,Tarnow L,Vlassara H,Parving HH,Cambien F

    更新日期:2001-05-01 00:00:00

  • Molecular detection of circulating beta-cells after islet transplantation.

    abstract::Islet transplantation is a promising treatment for type 1 diabetes. However, islet grafts are submitted to multiple injuries, including immunosuppressive drug toxicity, hyperglycemia, hypoxia, unspecific inflammatory reactions, as well as allo- and autoimmune destruction. Therapeutic approaches to these damage mechani...


    pub_type: 杂志文章


    authors: Ritz-Laser B,Oberholzer J,Toso C,Brulhart MC,Zakrzewska K,Ris F,Bucher P,Morel P,Philippe J

    更新日期:2002-03-01 00:00:00

  • Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes.

    abstract::Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate fou...


    pub_type: 杂志文章


    authors: Gregory JM,Kraft G,Scott MF,Neal DW,Farmer B,Smith MS,Hastings JR,Allen EJ,Donahue EP,Rivera N,Winnick JJ,Edgerton DS,Nishimura E,Fledelius C,Brand CL,Cherrington AD

    更新日期:2015-10-01 00:00:00

  • Glucose regulates the release of orexin-a from the endocrine pancreas.

    abstract::Orexins (hypocretins) are novel neuropeptides that appear to play a role in the regulation of energy balances. Orexin-A (OXA) increases food intake in rodents, and fasting activates OXA neurons in both the lateral hypothalamic area and gut. OXA is also found in the endocrine pancreas; however, little is known about it...


    pub_type: 杂志文章


    authors: Ouedraogo R,Näslund E,Kirchgessner AL

    更新日期:2003-01-01 00:00:00

  • Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are associated with plasma adiponectin.

    abstract::Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nu...


    pub_type: 杂志文章


    authors: Woo JG,Dolan LM,Deka R,Kaushal RD,Shen Y,Pal P,Daniels SR,Martin LJ

    更新日期:2006-02-01 00:00:00

  • Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells.

    abstract::In nonobese diabetic (NOD) mice, a deficiency in the number and function of invariant natural killer T-cells (iNKT cells) contributes to the onset of type 1 diabetes. The activation of CD1d-restricted iNKT cells by alpha-galactosylceramide (alpha-GalCer) corrects these deficiencies and protects against spontaneous and...


    pub_type: 杂志文章


    authors: Mi QS,Ly D,Zucker P,McGarry M,Delovitch TL

    更新日期:2004-05-01 00:00:00

  • Progression to islet destruction in a cyclophosphamide-induced transgenic model: a microarray overview.

    abstract::Type 1 diabetes appears to progress not as an uncontrolled autoimmune attack on the pancreatic islet beta-cells, but rather in a highly regulated manner. Leukocytic infiltration of the pancreatic islets by autoimmune cells, or insulitis, can persist for long periods of time before the terminal destruction of beta-cell...


    pub_type: 杂志文章


    authors: Matos M,Park R,Mathis D,Benoist C

    更新日期:2004-09-01 00:00:00

  • Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression.

    abstract::A 5-day culture of adult rat islets with human recombinant IL-1 beta (3 U/ml) resulted in the death of most alpha-cells and 50% of beta-cells. The IL-1--exposed islet tissue contained--in addition to poorly granulated beta-cells--patches of outgrowing monolayers and dispersed activated macrophages. In purified alpha- ...


    pub_type: 杂志文章


    authors: Ling Z,In't Veld PA,Pipeleers DG

    更新日期:1993-01-01 00:00:00

  • Body size and shape changes and the risk of diabetes in the diabetes prevention program.

    abstract::The researchers conducted this study to test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity. The Diabetes Prevention Program (DPP) recruited and randomized individuals with impaired glucose tolerance to treatment with placebo, metformin, or lifestyle modific...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Fujimoto WY,Jablonski KA,Bray GA,Kriska A,Barrett-Connor E,Haffner S,Hanson R,Hill JO,Hubbard V,Stamm E,Pi-Sunyer FX,Diabetes Prevention Program Research Group.

    更新日期:2007-06-01 00:00:00

  • Augmentation of the neutrophil respiratory burst through the action of advanced glycation end products: a potential contributor to vascular oxidant stress.

    abstract::An accelerated accumulation of advanced glycation end products (AGEs) occurs in diabetes secondary to the increased glycemic burden. In this study, we investigated the contribution of AGEs to intravascular oxidant stress by examining their action on the neutrophil burst of reactive oxygen species (ROS); this may be a ...


    pub_type: 杂志文章


    authors: Wong RK,Pettit AI,Davies JE,Ng LL

    更新日期:2002-09-01 00:00:00

  • Bactericidal properties of commercial U.S.P. formulated insulin.

    abstract::This study examined the suitability of commercial U.S.P. insulin as a bacterial growth medium. Purified port insulin (Iletin II, Eli Lilly & Co., Indianapolis, Indiana) was inoculated with approximately 500,000 bacteria per ml of: (1) Staphylococcus epidermidis, (2) Staphylococcus aureus, or (3) Escherichia coli. All ...


    pub_type: 杂志文章


    authors: Schade DS,Eaton RP

    更新日期:1982-01-01 00:00:00

  • IL12B polymorphism and type 1 diabetes in the Italian population: a case-control study.

    abstract::A polymorphism in the interleukin 12B gene was recently reported to be strongly associated with type 1 diabetes in 422 Australian and British families. We analyzed the same polymorphism in 470 Italian type 1 diabetic patients and 544 matched control subjects and found no evidence of association with the disease. ...


    pub_type: 杂志文章


    authors: Nisticò L,Giorgi G,Giordano M,Galgani A,Petrone A,D'Alfonso S,Federici M,Di Mario U,Pozzilli P,Buzzetti R,Cascino I

    更新日期:2002-05-01 00:00:00

  • Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus Study.

    abstract::It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro- and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleuki...


    pub_type: 杂志文章


    authors: van Exel E,Gussekloo J,de Craen AJ,Frölich M,Bootsma-Van Der Wiel A,Westendorp RG,Leiden 85 Plus Study.

    更新日期:2002-04-01 00:00:00

  • Resistin impairs insulin-evoked vasodilation.

    abstract:OBJECTIVE:Since vascular dysfunction is a main trait of obese subjects, in the present study we evaluated the vascular impact of resistin, a recently discovered hormone markedly increased in obesity. RESEARCH DESIGN AND METHODS:We performed our analysis on aortic and mesenteric segments from young and old C57BL/6 mice...


    pub_type: 杂志文章


    authors: Gentile MT,Vecchione C,Marino G,Aretini A,Di Pardo A,Antenucci G,Maffei A,Cifelli G,Iorio L,Landolfi A,Frati G,Lembo G

    更新日期:2008-03-01 00:00:00

  • MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.

    abstract::Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target ...


    pub_type: 杂志文章


    authors: Grieco FA,Sebastiani G,Juan-Mateu J,Villate O,Marroqui L,Ladrière L,Tugay K,Regazzi R,Bugliani M,Marchetti P,Dotta F,Eizirik DL

    更新日期:2017-01-01 00:00:00

  • Chronic reduction of plasma free fatty acid improves mitochondrial function and whole-body insulin sensitivity in obese and type 2 diabetic individuals.

    abstract::Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT) individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also has been described in insulin-resistant T2DM and obese subjects. We examined wheth...


    pub_type: 杂志文章


    authors: Daniele G,Eldor R,Merovci A,Clarke GD,Xiong J,Tripathy D,Taranova A,Abdul-Ghani M,DeFronzo RA

    更新日期:2014-08-01 00:00:00

  • Reduction and recovery of plasma 1,5-anhydro-D-glucitol level in diabetes mellitus.

    abstract::The plasma concentration of 1,5-anhydro-D-glucitol (AG) was measured in 135 newly diagnosed patients who were referred for oral glucose tolerance tests. AG concentrations in the nondiabetic patients indicated that the mean value of normal AG concentration was 21.8 micrograms/ml (SD = 5.9 micrograms/ml, range 9.6-38.8 ...


    pub_type: 杂志文章


    authors: Yamanouchi T,Akanuma H,Asano T,Konishi C,Akaoka I,Akanuma Y

    更新日期:1987-06-01 00:00:00

  • v- and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fat

    abstract::Insulin stimulation of adipose and muscle cells results in the translocation of GLUT4 from an intracellular location to the plasma membrane; this translocation is defective in insulin resistance. Studies have suggested an important role for synaptobrevin and syntaxin homologues in this event, particularly the v-solubl...


    pub_type: 杂志文章


    authors: Maier VH,Melvin DR,Lister CA,Chapman H,Gould GW,Murphy GJ

    更新日期:2000-04-01 00:00:00

  • Nonhuman primates as models for the study of human diabetes mellitus.

    abstract::Nonhuman primates have been used for a variety of studies on diabetes mellitus. Spontaneous, natural forms of diabetes have been well documented in several species; there are limited data on numerous other species that indicate diabetes or a diabetes-like syndrome. The causes and manifestations of spontaneous diabetes...


    pub_type: 杂志文章


    authors: Howard CF Jr

    更新日期:1982-01-01 00:00:00

  • Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control.

    abstract::Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experi...


    pub_type: 杂志文章


    authors: Rao AD,Bonyhay I,Dankwa J,Baimas-George M,Kneen L,Ballatori S,Freeman R,Adler GK

    更新日期:2016-01-01 00:00:00

  • Pathobiology of endothelial and other vascular cells in diabetes mellitus. Call for data.

    abstract::Because the pathogenetic understanding of diabetic vascular complications remains fragmentary, and even the best available interventions may prove insufficient to arrest the progression of certain lesions, new avenuses of investigation should be pursued. One of these should be the early in vivo investigation of the ce...


    pub_type: 杂志文章,评审


    authors: Lorenzi M,Cagliero E

    更新日期:1991-06-01 00:00:00

  • Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants.

    abstract::It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previou...


    pub_type: 临床试验,杂志文章


    authors: Butler PC,Kryshak EJ,Schwenk WF,Haymond MW,Rizza RA

    更新日期:1990-02-01 00:00:00

  • Changes in nerve conduction velocity after six weeks of glucoregulation with portable insulin infusion pumps.

    abstract::Near normal glucoregulation was maintained in 10 patients with insulin-dependent (type I) diabetes mellitus for 6 wk with preprogrammed continuous subcutaneous insulin infusion using a portable battery-powered infusion pump (CSII). This form of therapy resulted in a statistically significant increase in motor nerve co...


    pub_type: 杂志文章


    authors: Pietri A,Ehle AL,Raskin P

    更新日期:1980-08-01 00:00:00

  • Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM.

    abstract::Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric...


    pub_type: 杂志文章


    authors: Polonsky KS,Gumbiner B,Ostrega D,Griver K,Tager H,Henry RR

    更新日期:1994-07-01 00:00:00

  • Heterogeneity of the Human Pancreatic Islet.

    abstract::Pancreatic β-cells play a pivotal role in maintaining normoglycemia. Recent studies have revealed that the β-cell is not a homogeneous cell population but, rather, is heterogeneous in a number of properties such as electrical activity, gene expression, and cell surface markers. Identification of specific β-cell subpop...


    pub_type: 杂志文章


    authors: Dybala MP,Hara M

    更新日期:2019-06-01 00:00:00

  • Is cigarette smoking more frequent among insulin-treated diabetics?

    abstract::During epidemiologic investigations of vascular complications of diabetes in Warsaw the habit of cigarette smoking was analyzed in the subjects studied (4,530 diabetics). It was found that in the group of diabetics the number of ex-smokers was much greater (p less than 0.01) and that of present smokers lower (p less t...


    pub_type: 杂志文章


    authors: Czyzyk A,Królewski AS

    更新日期:1976-08-01 00:00:00

  • Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger β-Cell Failure.

    abstract::Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of...


    pub_type: 杂志文章


    authors: Triñanes J,Ten Dijke P,Groen N,Hanegraaf M,Porrini E,Rodriguez-Rodriguez AE,Drachenberg C,Rabelink TJ,de Koning E,Carlotti F,de Vries APJ

    更新日期:2020-02-01 00:00:00