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Am J Physiol Endocrinol Metab 256: E173-E178, 1989;
0193-1849/89 $5.00
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AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E173-E178, Copyright © 1989 by American Physiological Society

ARTICLES

alpha-Glycerophosphate shuttle in a clonal beta-cell line

M. D. Meglasson, K. M. Smith, D. Nelson and M. Erecinska
Diabetes Research Center, University of Pennsylvania School of Medicine, Philadelphia 19104.

It has been proposed that the alpha-glycerophosphate (alpha-GOP) shuttle plays a crucial role in regulation of glycolysis in beta-cells by linking reoxidation of cytosolic NADH to formation of ATP in the electron transport chain (J. Biol. Chem. 265: 8287, 1981). Direct evidence for this suggestion is still lacking, however. In this work the operation of the alpha-GOP shuttle was investigated in the insulin-secreting cell line HIT-T15. The constituent enzymes of the pathway were found to be present in HIT cells. Flavin-linked alpha-GOP dehydrogenase was associated with the mitochondrial fraction, whereas NAD+-dependent alpha-GOP dehydrogenase was localized in the cytosol. In the presence of amobarbital (used to preserve the function of the alpha-GOP shuttle under conditions where oxidation of NADH by the respiratory chain was blocked), glucose increased insulin secretion, O2 consumption, and the cell [ATP]/[ADP] when compared with amobarbital alone. These results indicate that the alpha-GOP shuttle contributes to ATP generation in HIT cells and that its activation may be necessary for the initiation of insulin secretion by glucose.


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Q. Gong, L. J. Brown, and M. J. MacDonald
Functional Analysis of Two Promoters for the Human Mitochondrial Glycerol Phosphate Dehydrogenase Gene
J. Biol. Chem., November 22, 2000; 275(48): 38012 - 38021.
[Abstract] [Full Text] [PDF]


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