Functional disturbance in the novel adenylyl cyclase signaling mechanism (ACSM) of insulin and relaxin action in rat streptozotocin (STZ) type I diabetes was studied on the basis of the authors' conception of molecular defects in hormonal signaling systems as the main causes of endocrine diseases. Studying the functional state of molecular components of the ACSM and the mechanism as a whole, the following changes were found in the skeletal muscles of diabetic rats compared with control animals: 1) increase of insulin receptor binding due to an increase in the number of insulin binding sites with high and low affinity; 2) increase of the basal adenylyl cyclase (AC) activity and the reduction of AC-activating effect of non-hormonal agents (guanine nucleotides, sodium fluoride, forskolin); 3) reduction of ACSM response to stimulatory action of insulin and relaxin; 4) decrease of the insulin-activating effect on the key enzymes of carbohydrate metabolism, glycogen synthase and glucose-6-phosphate dehydrogenase. Hence, the functional activity of GTP-binding protein of stimulatory type, AC and their functional coupling are decreased during experimental type 1 diabetes that leads to the impairment of the transduction of insulin and relaxin signals via ACSM.

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Insulin was isolated from the pancreas of Chondrostean fish, the Russian sturgeon, Acipenser guldenstaedti, by acid‐ethanol extraction followed by ion‐exchange and reverse‐phase high‐performance liquid chromatographies. The amino acid sequence determined by automated Edman degradation is as follows: A‐chain (21‐amino‐acid peptide), H‐Gly‐Ile‐Val‐Glu‐Gln‐Cys‐Cys‐His‐Ser‐Pro‐Cys‐Ser‐Leu‐Tyr‐Asp‐Leu‐Glu‐Asn‐Tyr‐Cys‐Asn‐OH; and B‐chain (31‐amino‐acid peptide), H‐Ala‐Ala‐Asn‐Gln‐His‐Leu‐Cys‐Gly‐Ser‐His‐Leu‐Val‐Glu‐Ala‐Leu‐Tyr‐Leu‐Val‐Cys‐Gly‐Glu‐Arg‐Gly‐Phe‐Phe‐Tyr‐Thr‐Pro‐Asn‐Lys‐Val‐OH. The sturgeon insulin appears to be identical with one of two forms of paddlefish insulin and differs from the other form by a single substitution in the A‐chain, Asp15: His15. The amino acid sequence of sturgeon insulin is more similar to the amino acid sequence of mammalian insulins than of other fish insulins. Sturgeon insulin showed parallel but weaker displacement than porcine insulin and pink salmon insulin in their respective radioimmunoassays and was less potent than porcine insulin in displacing radiolabeled porcine insulin bound to partially purified rat liver plasma membranes.

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