title: The glucose sensor in HIT cells is the glucose transporter.
abstract: The nature of the rate-limiting step for glucose utilization by the clonal insulin-producing cell line HIT-T15 has been investigated. In contrast to the situation in islets of Langerhans, we find that the HIT cell glucose metabolism is limited by the rate of entry of glucose into the cell. This is evidenced by the low rate of sugar transport and by the marked reduction in the rate of glucose utilization elicited by inhibitors of the glucose transporter. As judged by competition with glucose, the HIT cell glucose transporter also transports mannose, 2-deoxyglucose and 3-O-methylglucose but not L-glucose or N-acetylglucosamine. The Km for glucose of the glucose transporter, measured as the concentration of glucose required for a half-maximal rate of glucose utilization, is 4.3 mM, similar to the concentration reported to give half-maximal insulin release. Glucose-stimulated insulin release from HIT cells is inhibited by phloretin or cytochalasin B but not by mannoheptulose. We conclude that the secretory responses of HIT cells are consistent with the substrate-site hypothesis, but that, in contrast to normal B-cells, the glucose sensor which confers concentration-dependence and specificity to sugar-stimulated insulin release, is the glucose transporter.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ashcroft
authors.forename: M
authors.initials: M
authors.lastname: Stubbs
mesh_terms: D019325:3-O-Methylglucose; D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D007515:Islets of Langerhans; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D013395:Sucrose; D005947:Glucose