Uptake of D-mannoheptulose by normal and tumoral pancreatic islet cells

D-mannoheptulose was recently proposed as a possible tool to label preferen tially insulin-producing cells in the pancreatic gland. In the present stud y, D-[H-3]-mannoheptulose uptake by rat pancreatic islets or dispersed isle t cells was found to represent a time-related and temperature-sensitive pro cess inhibited by cytochalasin B. This mould metabolite also inhibited the efflux of D-[H-3]mannoheptulose from prelabelled islets. After 60 min incub ation at 37 degreesC, the apparent intracellular distribution space of the tritiated heptose was close to or somewhat higher than that of D-[5-H-3]]gl ucose and close to 50% of the intracellular (HOH)-H-3 space. It was further enhanced by D-glucose and a high concentration of 10 mM of D-mannoheptulos e. The uptake of D-[3H]mannoheptulose was much lower however than that of D -[H-3]mannoheptulose hexaacetate. As judged from the fate of D-mannoheptulo se hexa[2-C-14]acetate, the latter ester was efficiently hydrolyzed in the islet cells. The internalization of D-[H-3]mannoheptulose (or its eater) co incided with the generation of tritiated acidic metabolites, reflecting pho sphorylation of the heptose. The situation found in normal islet cells shar ply differed from that found in tumoral islet cells of either the RINm5F or INS-1 line, in which the apparent distribution space of D-[H-3]mannoheptul ose represented only about 3 and 9%, respectively, of the intracellular (HO H)-H-3 space. These results indicate that the entry of D-mannoheptulose int o islet cells represents a carrier-mediated process, possibly mediated at t he intervention of GLUT2 and, hence, provide further support to the possibl e use of a. suitable D-mannoheptulose analog as a tool for the preferential labelling of insulin-producing; cells in the pancreatic gland.