Insulin in Invertebrates and Cyclostomes

It seems increasingly clear that insulin is a hormone that doesnot occur exclusively in vertebrates. Several independent reportsnow exist giving evidence of insulin production in the digestivetissues of both deuterostomian and protostomian invertebrates.Cells with some light-microscopical and ultrastructural characteristicsof vertebrate B-cells have also been observed. Recently, evidencehas 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 positionin the comparative endocrinology of the islet parenchyma andin the evolution of insulin production. It may represent anevolutionary link between the presumably gut-connected dispersedinsulin-producing cells of deuterostomian invertebrates andthe pancreatic islets of gnathostomian vertebrates. This hypothesiswas supported by the fact that cells with light-microscopicaland ultrastructural similarities to the islet B-cells were observedin the bile duct mucosa of the hagfish, Myxine glutinosa. However,immunofluorescent studies with antisera against human insulinand C-peptide did not show any immunoreactive material outsidethe B-cells of the endocrine pancreas. Particular attentionwas paid to elucidate the biological significance of the largecystic cavities that are so typical for the cyclostomian isletparenchyma. The working hypothesis that they may contain storedinsulin, proinsulin (or even "proto-proinsulin") was not supportedby immunofluorescence, autoradiographic, or ultrastructuralinvestigations, nor by proinsulin assays. It is possible thathagfish islet B-cells contain zinc, despite the fact that theamino acid residue in B₁₀-position is aspartic acid insteadof histidine. The biosynthesis of hagfish insulin shows a patternsimilar to that in gnathostomes. Its rate is related to theambient temperature and at 11 C the conversion of proinsulinto insulin lasts several days.