Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1432-0428
    Keywords: Ca2+-activated K-channel ; pancreatic Beta cell ; HIT T15 cell ; insulin-secreting cell line ; planar lipid bilayer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study evaluates the use of the planar lipid bilayer as a functional assay of Ca2+-activated K+ channel activity for use in purification of the channel protein. Ca2+-activated K+ channels from the plasma membrane of an insulin-secreting hamster Beta-cell line (HIT T15) were incorporated into planar lipid bilayers. The single channel conductance was 233 picoSiemens (pS) in symmetrical 140 mmol/l KCl and the channel was strongly K+-selective (pCl/pK=0.046; PNa/PK=0.027). Channels incorporated into the bilayer with two orientations. In 65 % of cases, the probability of the channel being open was increased by raising calcium on the cis side of the bilayer (to which the membrane vesicles were added) or by making the cis side potential more positive. At a membrane potential of + 20 mV, which is close to the peak of the Beta-cell action potential, channel activity was half-maximal at a Ca2+ concentration of about 15 μmol/l. Charybdotoxin greatly reduced the probability of the channel being open when added to the side opposite to that at which Ca2+ activated the channel. These results resemble those found for Ca2+-activated K+ channels in native Beta cell membranes and indicate that the channel properties are not significantly altered by incorporation in a planar lipid bilayer.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-0428
    Keywords: Keywords ATP-sensitive K-current ; glucokinase ; beta cell ; insulin secretion ; MODY.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One type of maturity-onset diabetes of the young (MODY2) is caused by mutations in the glucokinase gene, a key glycolytic enzyme in the beta cell and liver. Glucose fails to stimulate insulin secretion in mice in which the glucokinase gene has been selectively knocked out in the beta cell. We tested the hypothesis that this effect results from defective metabolic regulation of beta cell ATP-sensitive potassium (KATP) channels. Glucose had little effect on KATP currents in homozygous (-/-) mice but inhibited KATP currents in wild-type (+/+) and heterozygous ( + /-) mice with EC50 of 3.2 mM and 5.5 mM, respectively, in newborn animals, and of 4.7 mM and 9.9 mM, respectively, in 1.5-year-old mice. Glucose (20 mmol/l) did not affect the resting membrane potential of -/- beta cells but depolarised wild-type and + /- beta cells and induced electrical activity. In contrast, 20 mmol/l ketoisocaproic acid or 0.5 mmol/l tolbutamide depolarised all three types of beta-cell. These results support the idea that defective glycolytic metabolism, produced by a loss (-/- mice) or reduction ( + /- mice) of glucokinase activity, leads to defective KATP channel regulation and thereby to the selective loss, or reduction, of glucose-induced insulin secretion. [Diabetologia (1998) 41: 654–659]
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 42 (1999), S. 903-919 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 42 (1999), S. 845-848 
    ISSN: 1432-0428
    Keywords: Keywords ATP-sensitive K-channel ; gliclazide ; sulphonylureas ; Kir6.2 ; sulphonylurea receptor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To investigate the tissue specificity of gliclazide for cloned beta-cell, cardiac and smooth muscle ATP-sensitive K-channels (KATP channels). These channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart, SUR2B in smooth muscle). Methods. Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes, and channel activity was measured by recording macroscopic currents in giant inside-out membrane patches. Gliclazide was added to the intracellular membrane surface. Results. We reported previously that Kir6.2-SUR1 currents are blocked at two sites by tolbutamide: a high-affinity site on SUR1 and a low-affinity site on Kir6.2. We now show that gliclazide also inhibits beta-cell KATP channels at two sites: a high-affinity site, which is half-maximally blocked (K i) at 50 ± 7 nmol/l (n = 8) and a low-affinity site with a K i of 3.0 ± 0.6 mmol/l (n = 4). The high-affinity site on SUR1 was thus about 40-fold more sensitive to gliclazide than to tolbutamide (K i∼ 2 μmol/l). Cloned cardiac and smooth muscle KATP channels did not show high-affinity block by gliclazide. Kir6.2-SUR2A currents exhibited a single low-affinity site with a K i of 0.8 ± 0.1 mmol/l (n = 5), which is likely to reside on the Kir6.2 subunit. Conclusion/interpretation. Our results show that gliclazide is a sulphonylurea with high affinity and strong selectivity for the beta-cell type of KATP channel. [Diabetologia (1999) 42: 845–848]
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 40 (1997), S. 528-532 
    ISSN: 1432-0428
    Keywords: Keywordstrp1 ; Ca-release activated channel ; pancreatic beta cell ; MIN6 cell ; insulin secretion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion is stimulated by glucose, hormones and neurotransmitters. Both activation of a non-selective cation current and activation of a Ca2 + current in response to depletion of intracellular Ca2 + stores have been suggested to play a role in this stimulation. The properties of these currents resemble those reported for the Drosophila genes trp and trpl. Using the reverse transcription polymerase chain reaction and Northern blot analysis we found that of the six mammalian trp-related genes (trp1–6), only trp1 was expressed at high levels in the mouse insulinoma cell line MIN6. We cloned the murine homologue of human trp1 from MIN6 cells and identified four variants (α, β, γ and δ), generated by alternative splicing near the N-terminus of the protein. In vitro translation showed that only the α and β splice variants are efficiently expressed. The β variant is the dominant form in MIN6 cells (and probably in mouse pancreatic islets), whereas the α variant is the major type in the mouse brain. The β variant showed 99 % identity to the human homologue at the amino acid level. [Diabetologia (1997) 40: 528–532]
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 560 (1989), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 560 (1989), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 11 (1988), S. 97-118 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-0428
    Keywords: ATP-sensitive K-channel ; pancreatic B cell ; human islet ; sulphonylurea ; tolbutamide ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 μmol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 μmol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 412 (1988), S. 597-603 
    ISSN: 1432-2013
    Keywords: Ba2+ currents ; Single Ca2+ channel ; B-cell ; Dihydropyridines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Barium currents flowing through single Ca2+ channels were recorded from outside-out patches isolated from mouse pancreatic B-cells. Only one type of Ca2+ channel was observed. In 110 mM Ba2+, the single channel conductance was 24 pS (at negative membrane potentials) and the current amplitude at 0 mV was−0.7 pA. Channel openings were activated by depolarisations more positive than −30 mV and showed little inactivation during 200 ms pulses. Open times were increased by BAY K 8644 an decreased by micromolar Cd2+. Channel activity was subject to rundown in excised patches and little activity remained after 10 min. These properties resemble those of L-type Ca2+ channels in other tissues. It is suggested that this Ca2+ channel participates in the generation of the B-cell action potential and mediates the increase in Ca2+ influx required for insulin secretion.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...