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

• Published in: European journal of biochemistry Vol. 213; no. 1; pp. 359 - 365
• Main Authors: ELLIOTT, Austin C., TREBILCOCK, Richard, YATES, Allen P., BEST, Leonard
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.1993; Blackwell
• Subjects: Animals; Biological and medical sciences; Cell physiology; Cricetinae; Fundamental and applied biological sciences. Psychology; Glyceraldehyde - metabolism; Hydrogen-Ion Concentration; Insulin - metabolism; Insulinoma; Membrane Potentials; Molecular and cellular biology; Responses to growth factors, tumor promotors, other factors; Tumor Cells, Cultured; Calcium; Secretion; Insulinoma; Rodentia; Coupled transport; Metabolism; Insulin; Depolarization; Protein hormone; Vertebrata; Mammalia; Plasma membrane; Hamster
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1111/j.1432-1033.1993.tb17769.x

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 (α‐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 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.