Conformation and proteolysis of glucagon and insulin in surfactant and lipid solutions.
The effects of micelles of nonionic, zwitterionic, anionic and cationic surfactants and lipids on the conformation of glucagon and insulin have been investigated by circular dichroism and intrinsic protein fluorescence. The influence of these amphipathic compounds on the hydrolysis, monitored by HPLC, of glucagon and insulin by trypsin and chymotrypsin has also been studied. The alpha-helix content of glucagon was increased to a similar extent by all the micelles, irrespective of their charge and of whether they were synthetic surfactants or phospholipids. The amphipathic compounds always induced a blue-shift in the wavelength of maximum emission of fluorescence of glucagon of about 9 nm, whereas the fluorescence intensity was increased in some cases and decreased in others. The circular dichroism of insulin was also modified in some cases. Some amphipathic compounds protected glucagon against proteolysis by trypsin and chymotrypsin very markedly, whereas others did not protect at all or only slightly protected the hormone. Two hypotheses have been formulated to explain the different results. Hydrolysis of insulin was generally not influenced by surfactants and lipids.
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Istituto di Chimica degli Ormoni, C.N.R., Milan, Italy.
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D000838:Anions; D002412:Cations; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D002942:Circular Dichroism; D005934:Glucagon / Q000378:metabolism; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D012996:Solutions; D013501:Surface-Active Agents / Q000494:pharmacology*; D014357:Trypsin / Q000378:metabolism
D000838:Anions; D002412:Cations; D002593:Cetrimonium Compounds; D007328:Insulin; D008055:Lipids; D008244:Lysophosphatidylcholines; D012996:Solutions; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D005934:Glucagon; D002918:Chymotrypsin; D014357:Trypsin; D000077286:Cetrimonium