It seems increasingly clear that insulin is a hormone that does not occur exclusively in vertebrates. Several independent reports now exist giving evidence of insulin production in the digestive tissues of both deuterostomian and protostomian invertebrates. Cells with some light-microscopical and ultrastructural characteristics of vertebrate B-cells have also been observed. Recently, evidence has been obtained that insulin can act as a hypoglycemic hormone, promoting glycogen synthesis, also in a protostomian invertebrate, the gastropod mollusc, Strophocheilus oblongus . The endocrine pancreas of the cyclostomes occupies a key position in the comparative endocrinology of the islet parenchyma and in the evolution of insulin production. It may represent an evolutionary link between the presumably gut-connected dispersed insulin-producing cells of deuterostomian invertebrates and the pancreatic islets of gnathostomian vertebrates. This hypothesis was supported by the fact that cells with light-microscopical and ultrastructural similarities to the islet B-cells were observed in the bile duct mucosa of the hagfish, Myxine glutinosa . However, immunofluorescent studies with antisera against human insulin and C-peptide did not show any immunoreactive material outside the B-cells of the endocrine pancreas. Particular attention was paid to elucidate the biological significance of the large cystic cavities that are so typical for the cyclostomian islet parenchyma. The working hypothesis that they may contain stored insulin, proinsulin (or even “proto-proinsulin”) was not supported by immunofluorescence, autoradiographic, or ultrastructural investigations, nor by proinsulin assays. It is possible that hagfish islet B-cells contain zinc, despite the fact that the amino acid residue in B10-position is aspartic acid instead of histidine. The biosynthesis of hagfish insulin shows a pattern similar to that in gnathostomes. Its rate is related to the ambient temperature and at 11 C the conversion of proinsulin to insulin lasts several days.
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