Differences in the time course of the metabolic response of B and non-B pancreatic islet cells to D-glucose and metabolized or non-metabolized hexoseesters

The early (min less than or equal to 1) and late (min 45) changes in NAD(P) H fluorescence caused by alpha-D-glucose pentaacetate, beta-L-glucose penta acetate, and beta-D-galactose pentaacetate (1.7 mM each), alone or together with either L-leucine (10.0 mM) or D-glucose (8.3 mM), were monitored in p urified pancreatic B and non-B rat islet cells. Whilst D-glucose caused a r apid increase in the NAD(P)H signal in B-cells, but not so in non-B cells, alpha-D-glucose pentaacetate, but not the two other monosaccharide esters, rapidly augmented the NAD(P)II signal in both B and non-B cells. After 45 m in, the NAD(P)IQ signal was increased by either D-glucose in both B and non -B islet cells or alpha-D-glucose pentaacetate. At this late time, beta-L-g lucose pentaacetate also increased the NAD(P)H signal in B cells exposed to L-leucine, These findings emphasize the relevance of differences in the ti me course of D-glucose uptake by B and non-B islet cells as a determinant o f rapid changes in redox state. They also provide further support for the r ole of intracellular Ca2+ regulating the activity of key Ca2+-responsive mi tochondrial dehydrogenases. Last, they reinforce the view that the effects of hexose pentaacetates upon insulin and glucagon release entail a dual mod ality, linked either to the catabolism of their hexose moiety or to a direc t effect of the esters themselves upon a stereospecific receptor system. (C ) 1999 Academic Press.