Failure of glucose to elicit a normal secretory response in fetal pancreatic beta cells results from glucose insensitivity of the ATP-regulated K+ channels.

Abstract:

:Fetal pancreatic beta cells demonstrate a deficient insulin release in response to glucose, but the underlying mechanism at the cellular level is unknown. By using beta cells from 21-day fetal rats we made an attempt to clarify the mechanism(s) behind this reduced glucose response. In addition to measuring insulin release, glucose metabolism, and cellular ATP content, ATP-regulated K+ channels (G channels) and voltage-activated Ca2+ currents were investigated with the patch-clamp technique. It was thus demonstrated that the ATP-regulated K+ channels in fetal beta cells were not sensitive to glucose but otherwise had similar characteristics as those of adult beta cells. Also, the characteristics of the voltage-activated Ca2+ currents were similar in adult and fetal beta cells. However, as judged from measurements of both glucose oxidation and glucose utilization, glucose metabolism was impaired in fetal beta cells. In addition, there was no increase in the ATP content, even when the cells were stimulated for 30 min. It is therefore concluded that the attenuated glucose-induced insulin release in fetal pancreatic beta cells is due to an immature glucose metabolism resulting in impaired regulation of the ATP-sensitive K+ channels. These findings may be relevant to the understanding of the deficient stimulus-secretion coupling associated with non-insulin-dependent diabetes.

authors

Rorsman P,Arkhammar P,Bokvist K,Hellerström C,Nilsson T,Welsh M,Welsh N,Berggren PO

doi

10.1073/pnas.86.12.4505

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

4505-9

issue

12

eissn

0027-8424

issn

1091-6490

journal_volume

86

pub_type

杂志文章
  • Screening for overlapping bacterial artificial chromosome clones by PCR analysis with an arbitrary primer.

    abstract::In this article, we used PCR analysis with arbitrary primers (AP-PCR) to screen for overlapping bacterial artificial chromosome (BAC) clones and assembly of contigs. A rice BAC library with three genome equivalents was used to prepare pooled BAC DNA. Twenty-two arbitrary primers were used to survey the pooled BAC DNAs...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.10.5661

    authors: Xu J,Yang D,Domingo J,Ni J,Huang N

    更新日期:1998-05-12 00:00:00

  • Class II (B) general transcription factor (TFIIB) that binds to the template-committed preinitiation complex is different from general transcription factor BTF3.

    abstract::A class II (B) general transcription factor of 34 kDa has been purified from HeLa cells to apparent homogeneity. This factor appears to be transcription factor IIB (TFIIB), since it binds in vitro to template-committed preinitiation complexes formed between a template containing the TATA box/cap-site elements of the a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.1.397

    authors: Moncollin V,Fischer L,Cavallini B,Egly JM,Chambon P

    更新日期:1992-01-01 00:00:00

  • Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct.

    abstract::The primary DNA lesion induced by malondialdehyde, a byproduct of lipid peroxidation and prostaglandin synthesis, is 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrimido[1, 2-a]purin-10(3H)-one (M1G). When placed opposite cytosine (underlined) at neutral pH in either the d(GGTMTCCG).d(CGGACACC) or d(ATCGCMCGGCATG). d(C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.12.6615

    authors: Mao H,Schnetz-Boutaud NC,Weisenseel JP,Marnett LJ,Stone MP

    更新日期:1999-06-08 00:00:00

  • H2O2-induced uncoupling of bovine lens Na+,K+-ATPase.

    abstract::A 1-hr exposure of bovine lenses in organ culture to H2O2 concentrations in the range found in the aqueous fluid of patients with cataracts inhibits 86Rb+ influx. At 1 mM H2O2, complete inhibition was observed and further investigated. Membrane permeability is slightly decreased. Although lactate concentrations increa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.7.2044

    authors: Garner WH,Garner MH,Spector A

    更新日期:1983-04-01 00:00:00

  • Evidence for a biological role in photosynthesis for cytochrome b-559--a component of photosystem II reaction center.

    abstract::Absorbance changes in untreated intact leaf discs, produced upon excitation with high-intensity red light, were shown to be due to the photooxidation of cytochrome b-559. At low intensities (<100 W/m2), photooxidation was almost undetectable. Photooxidation occurred with a half-time of 4.3 sec and an extent of 0.64 mo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.23.9295

    authors: Canaani O,Havaux M

    更新日期:1990-12-01 00:00:00

  • Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis.

    abstract::Integrin alphanubeta3 is found on a subset of tumor blood vessels where it is associated with angiogenesis and malignant tumor growth. We designed an alphanubeta3-targeted nanoparticle (NP) encapsulating the cytotoxic drug doxorubicin (Dox) for targeted drug delivery to the alphanubeta3-expressing tumor vasculature. W...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803728105

    authors: Murphy EA,Majeti BK,Barnes LA,Makale M,Weis SM,Lutu-Fuga K,Wrasidlo W,Cheresh DA

    更新日期:2008-07-08 00:00:00

  • lambda Rap protein is a structure-specific endonuclease involved in phage recombination.

    abstract::Bacteriophage lambda encodes a number of genes involved in the recombinational repair of DNA double-strand breaks. The product of one of these genes, rap, has been purified. Truncated Rap proteins that copurify with the full-length form are derived, at least in part, from a rho-dependent transcription terminator locat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.23.13507

    authors: Sharples GJ,Corbett LM,Graham IR

    更新日期:1998-11-10 00:00:00

  • CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations.

    abstract::Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain. Failing human cardiomyocytes exhibit increased CaMKII and voltage-gated Ca(2+) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0913760107

    authors: Koval OM,Guan X,Wu Y,Joiner ML,Gao Z,Chen B,Grumbach IM,Luczak ED,Colbran RJ,Song LS,Hund TJ,Mohler PJ,Anderson ME

    更新日期:2010-03-16 00:00:00

  • Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model.

    abstract::Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1113729109

    authors: Hirayama T,Van de Bittner GC,Gray LW,Lutsenko S,Chang CJ

    更新日期:2012-02-14 00:00:00

  • High accuracy finite difference approximation to solutions of elliptic partial differential equations.

    abstract::A flexible finite difference method is described that gives approximate solutions of linear elliptic partial differential equations, Lu = G, subject to general linear boundary conditions. The method gives high-order accuracy. The values of the unknown approximation function U are determined at mesh points by solving a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.6.2541

    authors: Lynch RE,Rice JR

    更新日期:1978-06-01 00:00:00

  • Identification of the Fc gamma receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies.

    abstract::To characterize the region on human IgG1 responsible for its high-affinity interaction with the human Fc gamma receptor class I (Fc gamma RI), we have analyzed the binding properties of a series of genetically engineered chimeric antidinitrophenyl antibodies with identical murine antibody combining sites and hybrid Ig...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.20.9036

    authors: Chappel MS,Isenman DE,Everett M,Xu YY,Dorrington KJ,Klein MH

    更新日期:1991-10-15 00:00:00

  • Amantadine-induced conformational and dynamical changes of the influenza M2 transmembrane proton channel.

    abstract::The M2 protein of influenza A virus forms a transmembrane proton channel important for viral infection and replication. Amantadine blocks this channel, thus inhibiting viral replication. Elucidating the high-resolution structure of the M2 protein and its change upon amantadine binding is crucial for designing antivira...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711500105

    authors: Cady SD,Hong M

    更新日期:2008-02-05 00:00:00

  • Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

    abstract::Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diph...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.16.5122

    authors: Gould RJ,Murphy KM,Reynolds IJ,Snyder SH

    更新日期:1983-08-01 00:00:00

  • Ameiotic recombination in asexual lineages of Daphnia.

    abstract::Despite the enormous theoretical attention given to the evolutionary consequences of sexual reproduction, the validity of the key assumptions on which the theory depends rarely has been evaluated. It is often argued that a reduced ability to purge deleterious mutations condemns asexual lineages to an early extinction....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0606435103

    authors: Omilian AR,Cristescu ME,Dudycha JL,Lynch M

    更新日期:2006-12-05 00:00:00

  • Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes.

    abstract::Infected cell protein 0 (ICP0) of herpes simplex virus 1, a multifunctional ring finger protein, enhances the expression of genes introduced into cells by infection or transfection, interacts with numerous cellular and viral proteins, and is associated with the degradation of several cellular proteins. Sequences encod...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.022531599

    authors: Hagglund R,Van Sant C,Lopez P,Roizman B

    更新日期:2002-01-22 00:00:00

  • Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail.

    abstract::Hypercholesterolemia, high serum cholesterol in the form of LDL, is a major risk factor for atherosclerosis. LDL is mostly degraded in the liver after its cellular internalization with the LDL receptor (LDLR). This clathrin-mediated endocytosis depends on the protein autosomal recessive hypercholesterolemia (ARH), whi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114128109

    authors: Dvir H,Shah M,Girardi E,Guo L,Farquhar MG,Zajonc DM

    更新日期:2012-05-01 00:00:00

  • Climate-driven introduction of the Black Death and successive plague reintroductions into Europe.

    abstract::The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1412887112

    authors: Schmid BV,Büntgen U,Easterday WR,Ginzler C,Walløe L,Bramanti B,Stenseth NC

    更新日期:2015-03-10 00:00:00

  • Modification of microtubule steady-state dynamics by phosphorylation of the microtubule-associated proteins.

    abstract::Phosphorylation of purified microtubule-associated proteins (MAPs) inhibits the rate and extent of MAP-stimulated microtubule assembly. The extent of microtubule assembly is reduced as a result of a decrease in the fraction of tubulin polymerized, without a significant change in the critical protein concentration. The...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.6.3413

    authors: Jameson L,Caplow M

    更新日期:1981-06-01 00:00:00

  • Robust perfect adaptation in bacterial chemotaxis through integral feedback control.

    abstract::Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In biological systems, it is common for the response to an extracellular stimulus to return to its prestimulus value even in the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.9.4649

    authors: Yi TM,Huang Y,Simon MI,Doyle J

    更新日期:2000-04-25 00:00:00

  • p85β phosphoinositide 3-kinase subunit regulates tumor progression.

    abstract::PIK3R2 encodes a ubiquitous regulatory subunit (p85β) of PI3K, an enzyme that generates 3-polyphosphoinositides at the plasma membrane. PI3K activation triggers cell survival and migration. We found that p85β expression is elevated in breast and colon carcinomas and that its increased expression correlates with PI3K p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1118138109

    authors: Cortés I,Sánchez-Ruíz J,Zuluaga S,Calvanese V,Marqués M,Hernández C,Rivera T,Kremer L,González-García A,Carrera AC

    更新日期:2012-07-10 00:00:00

  • Cooperative foraging, productivity, and the central limit theorem.

    abstract::The central limit theorem is applied to group foraging to show an automatic and universal benefit to group living. This may explain the paradoxical inverse correlation between group size and per capita brood production in primitively eusocial insects and why only one of the five major lineages of social insects contai...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.1.36

    authors: Wenzel JW,Pickering J

    更新日期:1991-01-01 00:00:00

  • Curved DNA: design, synthesis, and circularization.

    abstract::Curved DNA molecules and unusually small circles have been obtained by ligation of synthetic 21-base precursors: (sequence in text). The ligation resulted in the formation of double-stranded oligo-(precursor)s possessing a strong 10.5-base-pair (bp) periodicity of the runs of adenines. Two-dimensional polyacrylamide g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.4.862

    authors: Ulanovsky L,Bodner M,Trifonov EN,Choder M

    更新日期:1986-02-01 00:00:00

  • Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells.

    abstract::DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1216894110

    authors: Izhar L,Ziv O,Cohen IS,Geacintov NE,Livneh Z

    更新日期:2013-04-16 00:00:00

  • Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of listeria monocytogenes.

    abstract::We have isolated, by molecular cloning and genetic complementation of a listeriolysin-negative mutant, a gene required for the expression of this virulence factor in Listeria monocytogenes. The mutant strain SLCC53, which was nonhemolytic and avirulent, harbored a deletion of 450 base pairs located approximately 1500 ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.21.8336

    authors: Leimeister-Wächter M,Haffner C,Domann E,Goebel W,Chakraborty T

    更新日期:1990-11-01 00:00:00

  • Evidence for the role of PrP(C) helix 1 in the hydrophilic seeding of prion aggregates.

    abstract::Prions are mammalian proteins (PrPs) with a unique pathogenic property: a nonendogenous isoform PrP(Sc) can catalyze conversion of the endogenous PrP(C) isoform into additional PrP(Sc). In this work, we demonstrate that PrP(C) helix 1 has certain properties (hydrophilicity, charge distribution) that make it unique amo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.20.11293

    authors: Morrissey MP,Shakhnovich EI

    更新日期:1999-09-28 00:00:00

  • Chicken triosephosphate isomerase complements an Escherichia coli deficiency.

    abstract::We present the sequence of full-length chicken triosephosphate isomerase (D-glyceraldehyde 3-phosphate ketol-isomerase, EC 5.3.1.1) mRNA based on the analysis of cDNA and genomic clones. To isolate cDNA clones encoding the enzyme, we screened a muscle cDNA library with radioactively labeled cDNA made from RNA that had...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.7.2014

    authors: Straus D,Gilbert W

    更新日期:1985-04-01 00:00:00

  • Retinoid X receptors are essential for early mouse development and placentogenesis.

    abstract::Embryos carrying null mutations of both retinoid X receptors alpha and beta (RXRalpha-/-/RXRbeta-/- mutants) were generated. These mutant embryos die between 9.5 and 10.5 days of gestation and display a wide range of abnormalities. The cause of the lethality appears to be the lack of formation of the labyrinthine zone...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.2.547

    authors: Wendling O,Chambon P,Mark M

    更新日期:1999-01-19 00:00:00

  • Changes in gamma-aminobutyrate type A receptor subunit mRNAs, translation product expression, and receptor function during neuronal maturation in vitro.

    abstract::The amounts of mRNAs encoding alpha 1, alpha 6, beta 2, beta 3, gamma 2, and delta subunits of gamma-aminobutyrate type A (GABAA) receptors and the gold immunolabeling density of their translation products were monitored during the growth of neonatal rat granule cells in primary culture. We investigated possible corre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.23.10952

    authors: Zheng TM,Zhu WJ,Puia G,Vicini S,Grayson DR,Costa E,Caruncho HJ

    更新日期:1994-11-08 00:00:00

  • Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease.

    abstract::Alzheimer's disease (AD), characterized by cognitive decline, has emerged as a disease of synaptic failure. The present study reveals an unanticipated role of erythropoietin-producing hepatocellular A4 (EphA4) in mediating hippocampal synaptic dysfunctions in AD and demonstrates that blockade of the ligand-binding dom...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1405803111

    authors: Fu AK,Hung KW,Huang H,Gu S,Shen Y,Cheng EY,Ip FC,Huang X,Fu WY,Ip NY

    更新日期:2014-07-08 00:00:00

  • Chimpanzee super strength and human skeletal muscle evolution.

    abstract::Since at least the 1920s, it has been reported that common chimpanzees (Pan troglodytes) differ from humans in being capable of exceptional feats of "super strength," both in the wild and in captive environments. A mix of anecdotal and more controlled studies provides some support for this view; however, a critical re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619071114

    authors: O'Neill MC,Umberger BR,Holowka NB,Larson SG,Reiser PJ

    更新日期:2017-07-11 00:00:00