5. THE ENDOCRINE PANCREAS
301
alloxan diabetes in teleosts is similar to that in mammals, despite some
differences in the biological action of mammalian and fish insulins (see
Sections 11, E, 1 and IV, B, 3 ) .
These conflicting results and varying interpretations do not permit a
general statement on the action of alloxan in teleosts. Species differences
in the sensitivity of the B cells to alloxan are well known in mammals and
may also play a role in teleosts (Murrel and Nace, 1959). Furthermore,
the method of blood sugar determination (Havu, 1969), as well as the
fishes’ response to handling, the manner of application of alloxan, its
quality and instability above pH 6, and the water temperature are factors
which must be considered in interpreting the available data (Falkmer,
1961). However, in some teleosts it appears that alloxan diabetes can be
elicited.
There are several theories on the mechanism of the B-cell destruction
by alloxan (cf. Falkmer, 1961; Cooperstein and Lazarow, 1964; Cooperstein et al., 1964). Lazarow’s “sulfhydryl theory” (1954) stimulated a
series of investigations on the mechanism of alloxan action; both in vim
and in vitro studies have been reported for teleosts (Falkmer, 1961,
1962a,b; Falkmer and Havu, 1964; cf. Lazarow, 1963). Lazarow and associates (Cooperstein and Lazarow, 1964; Cooperstein et al., 1964; Watkins et al., 1964a,b) conclude from recent studies on fish islets that alloxan
acts selectively on the cell membrane of the B cells. The permeability of
the cell membrane may be damaged at a site involved in sugar transport
(Watkins et al., 1968).
b. Other Cytotoleins. Several drugs have been reported to selectively
destroy the A cells in mammals and/or birds. Four of these drugs
(cobaltous chloride, Synthalin A, p-aminobensolsulfonamide isopropylthiodiazol ( IPTD ) , and sodium diethyldithiocarbamate) were tested in
fishes. Ermisch (1966) did not observe a specific effect of CoCl, on the
islet tissue of lampreys (Petromyzon planeri and Petromyzon fluviatilis) .
Likewise, Schirner (1963b) and Falkmer and Winbladh (1964b) failed
to achieve islet damage by application of CoCl, in Myxine. Schirner
(1963b) reports “A-cell lesions in Myxine after injection of Synthalin A;
these were not seen in the experiments of Falkmer and Winbladh
(1964b). Fodden (1956) did not obtain any islet changes in the toadfish
after CoCl, injections. However, in Scorpaena scrofu injections of CoCl,
and sodium diethyldithiocarbamate led to a decrease in the extractable,
hyperglycemic activity of the Brockmann bodies ( Mosca, 1959). Gambush holbrooki has a third type of islet cell ( D cell?) which is especially
sensitive to CoCl, (Ghiani and Federici, 1960). In his earlier investigations, Falkmer (1961) did not observe a cytotoxic effect of CoCl,, Synthalin A, or IPTD on the islets of Cottus scorpius. However, in subsequent
studies, Falkmer et al. (1964a,b) found that cobalt is selectively concen-
301
alloxan diabetes in teleosts is similar to that in mammals, despite some
differences in the biological action of mammalian and fish insulins (see
Sections 11, E, 1 and IV, B, 3 ) .
These conflicting results and varying interpretations do not permit a
general statement on the action of alloxan in teleosts. Species differences
in the sensitivity of the B cells to alloxan are well known in mammals and
may also play a role in teleosts (Murrel and Nace, 1959). Furthermore,
the method of blood sugar determination (Havu, 1969), as well as the
fishes’ response to handling, the manner of application of alloxan, its
quality and instability above pH 6, and the water temperature are factors
which must be considered in interpreting the available data (Falkmer,
1961). However, in some teleosts it appears that alloxan diabetes can be
elicited.
There are several theories on the mechanism of the B-cell destruction
by alloxan (cf. Falkmer, 1961; Cooperstein and Lazarow, 1964; Cooperstein et al., 1964). Lazarow’s “sulfhydryl theory” (1954) stimulated a
series of investigations on the mechanism of alloxan action; both in vim
and in vitro studies have been reported for teleosts (Falkmer, 1961,
1962a,b; Falkmer and Havu, 1964; cf. Lazarow, 1963). Lazarow and associates (Cooperstein and Lazarow, 1964; Cooperstein et al., 1964; Watkins et al., 1964a,b) conclude from recent studies on fish islets that alloxan
acts selectively on the cell membrane of the B cells. The permeability of
the cell membrane may be damaged at a site involved in sugar transport
(Watkins et al., 1968).
b. Other Cytotoleins. Several drugs have been reported to selectively
destroy the A cells in mammals and/or birds. Four of these drugs
(cobaltous chloride, Synthalin A, p-aminobensolsulfonamide isopropylthiodiazol ( IPTD ) , and sodium diethyldithiocarbamate) were tested in
fishes. Ermisch (1966) did not observe a specific effect of CoCl, on the
islet tissue of lampreys (Petromyzon planeri and Petromyzon fluviatilis) .
Likewise, Schirner (1963b) and Falkmer and Winbladh (1964b) failed
to achieve islet damage by application of CoCl, in Myxine. Schirner
(1963b) reports “A-cell lesions in Myxine after injection of Synthalin A;
these were not seen in the experiments of Falkmer and Winbladh
(1964b). Fodden (1956) did not obtain any islet changes in the toadfish
after CoCl, injections. However, in Scorpaena scrofu injections of CoCl,
and sodium diethyldithiocarbamate led to a decrease in the extractable,
hyperglycemic activity of the Brockmann bodies ( Mosca, 1959). Gambush holbrooki has a third type of islet cell ( D cell?) which is especially
sensitive to CoCl, (Ghiani and Federici, 1960). In his earlier investigations, Falkmer (1961) did not observe a cytotoxic effect of CoCl,, Synthalin A, or IPTD on the islets of Cottus scorpius. However, in subsequent
studies, Falkmer et al. (1964a,b) found that cobalt is selectively concen-