Uptake of D-mannoheptulose by normal and tumoral pancreatic islet cells.
D-mannoheptulose was recently proposed as a possible tool to label preferentially insulin-producing cells in the pancreatic gland. In the present study, D-[3H]-mannoheptulose uptake by rat pancreatic islets or dispersed islet cells was found to represent a time-related and temperature-sensitive process inhibited by cytochalasin B. This mould metabolite also inhibited the efflux of D-[3H]-mannoheptulose from prelabelled islets. After 60 min incubation at 37 degrees C, the apparent intracellular distribution space of the tritiated heptose was close to or somewhat higher than that of D-[5-3H]glucose and close to 50% of the intracellular 3HOH space. It was further enhanced by D-glucose and a high concentration of 10 mM of D-mannoheptulose. The uptake of D-[3H]mannoheptulose was much lower however than that of D-[3H]mannoheptulose hexaacetate. As judged from the fate of D-mannoheptulose hexa[2-14C]acetate, the latter ester was efficiently hydrolyzed in the islet cells. The internalization of D-[3H]mannoheptulose (or its ester) coincided with the generation of tritiated acidic metabolites, reflecting phosphorylation of the heptose. The situation found in normal islet cells sharply differed from that found in tumoral islet cells of either the RINm5F or INS-1 line, in which the apparent distribution space of D-[3H]mannoheptulose represented only about 3 and 9%, respectively, of the intracellular 3HOH space. These results indicate that the entry of D-mannoheptulose into islet cells represents a carrier-mediated process, possibly mediated at the intervention of GLUT2 and, hence, provide further support to the possible use of a suitable D-mannoheptulose analog as a tool for the preferential labelling of insulin-producing cells in the pancreatic gland.
Ramirez
R
R
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Rasschaert
J
J
Laghmich
A
A
Louchami
K
K
Nadi
A B
AB
Jijakli
H
H
Kadiata
M M
MM
Sener
A
A
Malaisse
W J
WJ
D000818:Animals; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008356:Mannoheptulose / Q000493:pharmacokinetics*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051381:Rats; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B; D008356:Mannoheptulose; D004247:DNA; D005947:Glucose