292
AUGUST EPPLE
tion granules of their preparations contained not only insulin and glucagon but other proteins as well.
All insulins studied so far consist of two polypeptide chains which are
linked by two disul6de bridges (cf. Eck and Dayhoff, 1966). Insulin can
be split into its A and B chains and resynthesized; it was even possible
to prepare cod and ox “hybrid” insulins by mutual exchange of the isolated chains (S. Wilson et al., 1962).
Two different ways have been proposed for the final step of insulin
synthesis. Lazarow and co-workers (cf. Lazarow, 1965) and Humbel
(1965) concluded from their own and other authors’ findings that insulin
is formed from separate chains which are joined together by oxidizing
sulfhydryl groups to disul6de bonds. For this process, Lazarow (1965)
postulated the existence of a specific enzyme, “insulin zipase.” However,
recent evidence from studies on the biosynthesis of mammalian insulin
favors a different alternative, namely, that insulin is derived from a large,
single-chain protein containing intrachain disulfide bonds. Division of this
“proinsulin” into two chains is accomplished by cleavage of peptide bonds
with resulting loss of the linking fraction of the original single-chain
molecule (cf. Steiner and Oyer, 1967; Steiner et al., 1967; Chance and
Ellis, 1968; Clark and Steiner, 1968; Frank and Veros, 1968; Tung and
Yip, 1968).
The islets of many vertebrates contain very high amounts of zinc (cf.
Maske et al., 1956; Logothetopoulos et al., 1964; Pihl, 1967). This metal
is usually found within the B cells, yet the duck (Runge et al., 1956;
Weitzel et al., 1956) and the rat (Logothetopoulos et al., 1964; Weiss,
1964) have a high zinc content in the A and/or D cells. The decrease in
zinc concentration during islet cell stimulation suggests a relation between
this metal and the islet hormones (cf. Maske, 1957; Logothetopoulos
et al., 1964; Weiss, 1964). Since insulin does not crystallize at physiological pH without heavy metals (Scott, 1934), zinc may be involved in
storage and release of this hormone. On the other hand, glucagon also
appears to have a high affinity for zinc (cf. Weiss, 1964).
In teleosts, high concentrations of zinc were found in the endocrine
pancreas ( Weitzel et al., 1953; Maske et al., 1956; J. Davidson, 1958).
Histochemical studies revealed that in Cottus scorpius it is located in the
islet region which contains B and D cells (Falkmer et al., 1964a,b), and
electron microscopically it was demonstrated within the B granules of
Cottus qmdricornis (Pihl, 1967). However, Maske et al. (1956) found
no correlations between the concentrations of zinc and insulin within subcellular fractions of the islets of Pleuronectidae, and J. Davidson (1959)
found abundant zinc in the degranulated islets of alloxan-treated toadfish.
AUGUST EPPLE
tion granules of their preparations contained not only insulin and glucagon but other proteins as well.
All insulins studied so far consist of two polypeptide chains which are
linked by two disul6de bridges (cf. Eck and Dayhoff, 1966). Insulin can
be split into its A and B chains and resynthesized; it was even possible
to prepare cod and ox “hybrid” insulins by mutual exchange of the isolated chains (S. Wilson et al., 1962).
Two different ways have been proposed for the final step of insulin
synthesis. Lazarow and co-workers (cf. Lazarow, 1965) and Humbel
(1965) concluded from their own and other authors’ findings that insulin
is formed from separate chains which are joined together by oxidizing
sulfhydryl groups to disul6de bonds. For this process, Lazarow (1965)
postulated the existence of a specific enzyme, “insulin zipase.” However,
recent evidence from studies on the biosynthesis of mammalian insulin
favors a different alternative, namely, that insulin is derived from a large,
single-chain protein containing intrachain disulfide bonds. Division of this
“proinsulin” into two chains is accomplished by cleavage of peptide bonds
with resulting loss of the linking fraction of the original single-chain
molecule (cf. Steiner and Oyer, 1967; Steiner et al., 1967; Chance and
Ellis, 1968; Clark and Steiner, 1968; Frank and Veros, 1968; Tung and
Yip, 1968).
The islets of many vertebrates contain very high amounts of zinc (cf.
Maske et al., 1956; Logothetopoulos et al., 1964; Pihl, 1967). This metal
is usually found within the B cells, yet the duck (Runge et al., 1956;
Weitzel et al., 1956) and the rat (Logothetopoulos et al., 1964; Weiss,
1964) have a high zinc content in the A and/or D cells. The decrease in
zinc concentration during islet cell stimulation suggests a relation between
this metal and the islet hormones (cf. Maske, 1957; Logothetopoulos
et al., 1964; Weiss, 1964). Since insulin does not crystallize at physiological pH without heavy metals (Scott, 1934), zinc may be involved in
storage and release of this hormone. On the other hand, glucagon also
appears to have a high affinity for zinc (cf. Weiss, 1964).
In teleosts, high concentrations of zinc were found in the endocrine
pancreas ( Weitzel et al., 1953; Maske et al., 1956; J. Davidson, 1958).
Histochemical studies revealed that in Cottus scorpius it is located in the
islet region which contains B and D cells (Falkmer et al., 1964a,b), and
electron microscopically it was demonstrated within the B granules of
Cottus qmdricornis (Pihl, 1967). However, Maske et al. (1956) found
no correlations between the concentrations of zinc and insulin within subcellular fractions of the islets of Pleuronectidae, and J. Davidson (1959)
found abundant zinc in the degranulated islets of alloxan-treated toadfish.