Dynamic membrane interaction and amyloid fibril formation of glucagon, melittin and human calcitonin.

Glucagon is a 29-amino acid peptide hormone secreted by pancreatic α-cells and interacts with specific receptors located in various organs. Glucagon tends to form gel-like fibril aggregates that are cytotoxic. It is important to reveal the glucagon-membrane interaction to understand activity and cytotoxicity of glucagon and glucagon oligomers. In this review, first glucagon-membrane interactions are described as morphological changes in dimyristoylphosphatidylcholine (DMPC) bilayers containing glucagon in acidic and neutral conditions as compared to the case of melittin. Second, fibril formation by glucagon in acidic solution is discussed in light of morphological and structural changes. Third, kinetic analysis of glucagon fibril formation was performed using a two-step autocatalytic reaction mechanism, as investigated in the case of human calcitonin. The first step is a nuclear formation, and the second step is an autocatalytic fibril elongation. Forth, fibril formation of glucagon inside glucagon-DMPC bilayers in neutral solution under near physiological condition is described.

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