Lipolytic and adenyl-cyclase-stimulating activity of glucagon 1-6: comparison with glucagon derivatives chemically modified in the 7-29 sequence.
Glucagon 1-6 has a maximum lipolytic activity (Lmax) in the rat adipocyte which is 66% of that of glucagon. The N epsilon-guanidyl derivative, modified at Lys12, has about the same Lmax as glucagon 1-6. Modifying the carboxyl groups of glucagon with glycinamide or removing the COOH-terminal residues with cyanogen bromide reduces Lmax to less than 25% of the level of glucagon. The potency of each of these analogs (A50) in microM is as follows: glucagon 6 X 10(-3); glucagon 1-6 2 X 10(-2); N epsilon-guanidyl glucagon 9 X 10(-3); glycinamide glucagon 10(-2); cyanogen bromide peptide of glucagon 2 X 10(-1). The ability of all of the glucagon analogs to stimulate adenyl cyclase was somewhat less than their lipolytic activities with the exception of the glycinamide derivative and the cyanogen bromide peptide, which were slightly more active in stimulating adenyl cyclase than in lipolysis. Glucagon 1-6 is much more potent in stimulating adipocyte than liver adenyl cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003488:Cyanogen Bromide; D005934:Glucagon / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; C036296:glucagon (1-6); D005934:Glucagon; D000262:Adenylyl Cyclases; D003488:Cyanogen Bromide