Please use this identifier to cite or link to this item: https://doi.org/10.1016/S0006-2952(97)00057-9
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dc.titleInhibition of calcium-induced insulin secretion from intact HIT-T15 or INS-1β cells by GTP depletion
dc.contributor.authorMeredith, M.
dc.contributor.authorLi, G.
dc.contributor.authorMetz, S.A.
dc.date.accessioned2014-11-28T07:56:57Z
dc.date.available2014-11-28T07:56:57Z
dc.date.issued1997-06-15
dc.identifier.citationMeredith, M., Li, G., Metz, S.A. (1997-06-15). Inhibition of calcium-induced insulin secretion from intact HIT-T15 or INS-1β cells by GTP depletion. Biochemical Pharmacology 53 (12) : 1873-1882. ScholarBank@NUS Repository. https://doi.org/10.1016/S0006-2952(97)00057-9
dc.identifier.issn00062952
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/112801
dc.description.abstractUsing intact rat islets, we previously observed that GTP depletion(achieved through the use of mycophenolic acid or other synthesis inhibitors) impedes nutrient- but not K+ -induced insulin secretion. It was concluded that a proximal nutrient-dependent step in stimulus-secretion coupling (but not the process of Ca2+-induced exocytosis itself) is modulated by ambient GTP levels. To examine Ca2+-dependent steps further in intact β cells, INS-1 cells (which synthesize GTP and ATP similarly to rat islets) and HIT-T15 cells (whose synthesis of purine nucleotides is different) were studied following cell culture for 1-18 hr in various concentrations of mycophenolic acid (MPA) or mizoribine (MZ). Both agents profoundly reduced GTP content (mean: -78%) and lowered the GTP/GDP ratio by an average of -73%; concomitantly, MPA or MZ reduced insulin secretion induced by 10 mM glucose, 30 or 40 mM KCl, or 100 μM tolbutamide, independent of any changes in cell viability, insulin content. ATP content, the ATP/ADP ratio, or cytosolic free Ca2+ concentrations. In INS-1 cells (which appear to have normal nucleobase transport and 'salvage' pathway activities), guanine (but not adenine) restored GTP content, the GTP/GDP ratio, and Ca2+-induced secretion. In HIT cells, the phosphoribosylation of exogenous guanine or hypoxanthine is defective; however, provision of 500 μM guanosine (but not adenosine) reversed the effects of MPA. We conclude that at least in certain situations, a requisite role for GTP in the distal step(s) of exocytosis can be demonstrated.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/S0006-2952(97)00057-9
dc.sourceScopus
dc.subjectAdenine
dc.subjectCa2+
dc.subjectExocytosis
dc.subjectGTP
dc.subjectGuanine
dc.subjectInsulin secretion
dc.subjectMycophenolate
dc.typeArticle
dc.contributor.departmentNATIONAL UNIVERSITY MEDICAL INSTITUTES
dc.description.doi10.1016/S0006-2952(97)00057-9
dc.description.sourcetitleBiochemical Pharmacology
dc.description.volume53
dc.description.issue12
dc.description.page1873-1882
dc.description.codenBCPCA
dc.identifier.isiutA1997XN78000012
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