288
AUGUST EPPLE
Weitzel et al., 1967). In the 4-point mouse diaphragm assay, hagfish insulin shows lower potency than teleost insulins (Falkmer and Wilson,
1967). Studies on the structure revealed that the N-terminal amino acids
are glycine (A chain) and probably a basic amino acid (B chain). The
A chain contains no phenylalanine; one histidine of the B chain of other
known insulins is replaced by a different amino acid. The intact molecule,
and especially the A chain, is more basic than heretofore known insulins
( Weitzel et al., 1967).
In the lamprey, Petromyzon pluneri, Ermisch (1965) found strong
hypoglycemic activity of the islet extracts of both larval and adult animals
(mouse convulsion test). On the other hand, the hemagglutination inhibition test gave evidence of an immunological difference from bovine insulin. High doses of mammalian insulin induce a long-lasting hypoglycemia in Petromyzon fluviatilis (Leibson and Plisetskaya, 1967; cf.
Plisetskaya, 1967). In contrast to the situation in mammals, mammalian
insulin did not affect muscle glycogen, although it did increase liver
glycogen (Bentley and Follett, 1965).
b. Chondrichthyes. In 1922, Macleod showed that dogfish pancreata
contain an acid-ethanol extractable substance capable of causing hypoglycemia in rabbits. Recent studies of Patent (1968) revealed that bovine,
dogfish, and ratfish (Hydrolugus) insulins are effective hypoglycemic
agents in both dogfish, Squalus acanthias, and ratfish, Hydrolugus colliei.
Blood glucose levels in dogfish treated with their own insulin returned to
normal 3 days following peak hypoglycemia. Dogiish, injected with
bovine or ratfish insulins, remained hypoglycemic. Because of the poor
condition of the ratfish, it was not possible to determine the duration of
the hypoglycemia in this species. Antigenically, shark insulins were found
to be different both from ox and codfish insulins in biological and immunological tests; in the passive cutaneous anaphylactic test, the insulin
of Squalus reacted preferentially with antiserum to chicken insulin
(Wilson, 1966; Falkmer and Wilson, 1967; Falkmer, 1969).
c. Actinopterygii. According to Falkmer and Wilson (1967), the insulin of the holostean Amiu has very low potency in the 4point mouse
diaphragm assay. However, it was readily neutralized by both ox and codfish antiinsulin sera, suggesting that it has an antibody-combining site in
common with both of them. The results of the passive cutaneous anaphylactic test are in agreement with this (Wilson, 1966; Falkmer and Wilson,
1967).
The hypoglycemic action of teleost insulins in mammals is well known
( McCormick and Noble, 1925; Vincent et al., 1925) as is the hypoglycemic effect of mammalian insulin in fishes (see Section IV, C, 1, a ) ,
AUGUST EPPLE
Weitzel et al., 1967). In the 4-point mouse diaphragm assay, hagfish insulin shows lower potency than teleost insulins (Falkmer and Wilson,
1967). Studies on the structure revealed that the N-terminal amino acids
are glycine (A chain) and probably a basic amino acid (B chain). The
A chain contains no phenylalanine; one histidine of the B chain of other
known insulins is replaced by a different amino acid. The intact molecule,
and especially the A chain, is more basic than heretofore known insulins
( Weitzel et al., 1967).
In the lamprey, Petromyzon pluneri, Ermisch (1965) found strong
hypoglycemic activity of the islet extracts of both larval and adult animals
(mouse convulsion test). On the other hand, the hemagglutination inhibition test gave evidence of an immunological difference from bovine insulin. High doses of mammalian insulin induce a long-lasting hypoglycemia in Petromyzon fluviatilis (Leibson and Plisetskaya, 1967; cf.
Plisetskaya, 1967). In contrast to the situation in mammals, mammalian
insulin did not affect muscle glycogen, although it did increase liver
glycogen (Bentley and Follett, 1965).
b. Chondrichthyes. In 1922, Macleod showed that dogfish pancreata
contain an acid-ethanol extractable substance capable of causing hypoglycemia in rabbits. Recent studies of Patent (1968) revealed that bovine,
dogfish, and ratfish (Hydrolugus) insulins are effective hypoglycemic
agents in both dogfish, Squalus acanthias, and ratfish, Hydrolugus colliei.
Blood glucose levels in dogfish treated with their own insulin returned to
normal 3 days following peak hypoglycemia. Dogiish, injected with
bovine or ratfish insulins, remained hypoglycemic. Because of the poor
condition of the ratfish, it was not possible to determine the duration of
the hypoglycemia in this species. Antigenically, shark insulins were found
to be different both from ox and codfish insulins in biological and immunological tests; in the passive cutaneous anaphylactic test, the insulin
of Squalus reacted preferentially with antiserum to chicken insulin
(Wilson, 1966; Falkmer and Wilson, 1967; Falkmer, 1969).
c. Actinopterygii. According to Falkmer and Wilson (1967), the insulin of the holostean Amiu has very low potency in the 4point mouse
diaphragm assay. However, it was readily neutralized by both ox and codfish antiinsulin sera, suggesting that it has an antibody-combining site in
common with both of them. The results of the passive cutaneous anaphylactic test are in agreement with this (Wilson, 1966; Falkmer and Wilson,
1967).
The hypoglycemic action of teleost insulins in mammals is well known
( McCormick and Noble, 1925; Vincent et al., 1925) as is the hypoglycemic effect of mammalian insulin in fishes (see Section IV, C, 1, a ) ,