title: Effects of guanosine 3',5'-monophosphate on glucose utilization in isolated islets of Langerhans.
abstract: Dynamic changes in total glucose utilization in isolated islets of Langerhans of the rat were determined by quantitation of the formation of 3H2O from D-[5-3H]glucose. The addition of 8-bromo-cGMP (8-Br-cGMP) or monobutyryl cGMP to the islets during a linear phase of glucose utilization resulted in concentration- and time-dependent increases in glucose utilization. Effects of the analogs of cGMP on glucose utilization were noted as early as 5 min after the onset of stimulation in the presence of 10 mM glucose. 8-Br-cGMP also increased the utilization of 1 mM glucose within 20 min. Stimulatory effects of 8-Br-cGMP were observed in the presence of cycloheximide or N-acetylglucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) nor monobutyryl cAMP induced significant changes in glucose utilization at 1 or 10 mM glucose. In the presence of 3-isobutyl-1-methylxanthine (IBMX), 8-Br-cGMP, but not 8-Br-cAMP, induced a rapid change in glucose utilization. N-Methyl-N'-nitro-N-nitrosoguanidine, which activates guanylate cyclase, also stimulated glucose utilization in the presence of IBMX by 3-fold. IBMX alone did not change glucose utilization. In contrast, 8-Br-5'-GMP reduced glucose utilization, whereas 8-bromoinosine 3',5'-monophosphate and 8-bromoguanosine did not change glucose utilization. Sodium bromide did not affect glucose utilization. Glucose-stimulated insulin release was potentiated by 8-Br-cGMP, whereas insulin release from islets incubated in the absence of glucose or the presence of glyceraldehyde or 2-ketoisocaproic acid was not altered by 8-Br-cGMP. Thus, glucose utilization in pancreatic islets is modulated by cGMP, and the secretory response to 8-Br-cGMP is glucose dependent.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000117:Acetylglucosamine / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008769:Methylnitronitrosoguanidine; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; D008353:Mannitol; C040016:monobutyryl cyclic GMP; D003513:Cycloheximide; D006152:Cyclic GMP; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine; D000117:Acetylglucosamine