Glucagon structure-function relationships using isolated rat hepatocytes.
The ability of glucagon and several of its semi-synthetic analogues to stimulate glucose production in isolated rat hepatocytes was measured and compared for relative potencies. The order of decreasing biological activities of glucagon in this assay was as follows: glucagon greater than [HArg12]-glucagon greater than [des-Asn28, Thr29][homoserinehydrazide27]-glucagon approx. equal to [des-His1]-glucagon greater than [des-Asn28, Thr29][homoserinelactone27]-glucagon greater than [des-Asn28, Thr29]-[n-butylhomoserineamide27]-glucagon greater than glucagon1-21. Qualitatively, these results are similar to those obtained previously in the hepatic plasma membrane adenylate cyclase assay. Minor exceptions were noted for the hydrazide derivative and the partial agonist [des-His1]-glucagon, both of which were slightly more potent relative to glucagon in the glycogenolytic assay than in the adenylate cyclase assay. The assay provides important insight into glucagon structure-function relationships.
D000595:Amino Acid Sequence; D000818:Animals; D005934:Glucagon / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship
D005934:Glucagon