STIMULATION OF HIT-T15 INSULINOMA CELLS BY GLYCERALDEHYDE DOES NOT REQUIRE ITS METABOLISM

被引:17
作者
ELLIOTT, AC [1 ]
TREBILCOCK, R [1 ]
YATES, AP [1 ]
BEST, L [1 ]
机构
[1] MANCHESTER ROYAL INFIRM,DEPT PHYSIOL SCI,OXFORD RD,MANCHESTER M13 9WL,LANCS,ENGLAND
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1993年 / 213卷 / 01期
关键词
D O I
10.1111/j.1432-1033.1993.tb17769.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Rb-86+ 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 (pH(i)) 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.
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页码:359 / 365
页数:7
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