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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Stimulation of HIT-T15 insulinoma cells by glyceraldehyde does not require its metabolism.

The addition of the triose D-glyceraldehyde (5-20 mM) to HIT-T15 hamster insulinoma cells caused a rapid, marked depolarisation of the plasma membrane accompanied by a pronounced intracellular acidification, an increase in the cytosolic free calcium concentration [Ca2+]i and enhanced secretion of insulin. D-glyceraldehyde did not reduce the rate of efflux of 86Rb+ from loaded perifused cells. All of the above effects of D-glyceraldehyde were also observed in response to L-glyceraldehyde. The changes in membrane potential and intracellular pH (pHi) caused by D-glyceraldehyde were unaffected by the glycolytic inhibitor iodoacetate, by K(+)-channel blockers (tolbutamide and tetraethylammonium), or by inhibitors of the transport of lactate (alpha-fluorocinnamate), alanine (methylaminoisobutyrate) or glucose (phloretin, phlorrizin). The glyceraldehyde-induced depolarisation and acidification were also observed in the absence of extracellular Ca2+ or Na+. The increase in [Ca2+]i evoked by D-glyceraldehyde was reversed by removal of Ca2+ from the medium. The formation of lactate by HIT-T15 cells was not significantly increased by addition of 10 mM D-glyceraldehyde or L-glyceraldehyde. In contrast, 10 mM glucose caused an approximately fourfold rise in lactate production. The oxidation of D-glyceraldehyde by HIT-T15 cells was also extremely modest compared to glucose oxidation by these cells. These results suggest that the stimulation of HIT-T15 cells by either D-glyceraldehyde of L-glyceraldehyde does not require metabolism of the triose within the cell and may not involve closure of nucleotide-sensitive K+ channels. We propose that the electrogenic transport of glyceraldehyde across the plasma membrane, possibly via H+ cotransport, might lead to depolarisation and hence to Ca2+ entry into the cell.[1]

References

  1. Stimulation of HIT-T15 insulinoma cells by glyceraldehyde does not require its metabolism. Elliott, A.C., Trebilcock, R., Yates, A.P., Best, L. Eur. J. Biochem. (1993) [Pubmed]
 
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