PURIFICATION AND CHARACTERIZATION OF ISLET HORMONES (INSULIN, GLUCAGON, PANCREATIC-POLYPEPTIDE AND SOMATOSTATIN) FROM THE BURMESE PYTHON, PYTHON MOLURUS

Insulin was purified from an extract of the pancreas of the Burmese py thon, Python molurus (Squamata:Serpentes) and its primary structure es tablished as: A Chain: )-Cys-Ser-Leu-Tyr-Glu-Leu-Glu-Asn-Tyr-Cys(20)-A sn. B-Chain: y(20)-Asp-Arg-Gly-Phe-Tyr-Tyr-ser-pro-Arg-Ser(30). With t he exception of the conservative substitution Phe-->Tyr at position B2 5, those residues in human insulin that comprise the receptor-binding and those residues involved in dimer and hexamer formation are fully c onserved in python insulin. Python insulin was slightly more potent (1 .8-fold) than human insulin in inhibiting the binding of [[I-125-Tyr-A 14] insulin to the soluble full-length recombinant human insulin recep tor but was slightly less potent (1.5-fold) than human insulin for inh ibiting binding to the secreted extracellular domain of the receptor. The primary structure of python glucagon contains only one amino acid substitution (Ser(28)-->Asn) compared with turtle/duck glucagon and py thon somatostatin is identical to that of mammalian somatostatin-14. I n contrast, python pancreatic polypeptide n-Tyr-Leu-Asn-Ser-Ile(30)-As n-Arg-Pro-Arg-Phe.NH2) contains only 35 instead of the customary 36 re sidues and the amino acid sequence of this peptide has been poorly con served between reptiles and birds (18 substitutions compared with alli gator and 20 substitutions compared with chicken). (C) 1997 Elsevier S cience B.V.