Murlin, Clough, Gibbs, and Stokes 261
The first comparisons were made between subcutaneous and intravenous
administration, and between acid and alcoholic extracts. Extract 21,
used with both these dogs, was prepared from dog's pancreas by maceration
with ground glass in 0.2 N HCl. The number in parentheses (1) and (2)
in our system refers to the extraction. Thus No. 21 (2) is a second extrac-
tion of the same pancreatic tissue as was used in No. 21 (1). Usually a dog's
pancreas weighing 25 to 30 gm. was extracted in 250 cc. of the acid. The
first dose of 25 cc. of Extract 21, prepared as just described, when given
to Dog 1 intravenously, lowered the blood sugar within 3 hours to half its
original level and a second dose of 20 cc. given subcutaneously at 12 m.
brought down the sugar by 4 p.m. nearly to normal (0.144). The D:N ratio
was not established early in the day, but at 11.46 a.m. it was 2.18, and at
3.55 p.m. it was 2.14. There was up to this time, therefore, no perceptible
change. In the night urine, however, as determined next morning there was
but a small quantity of sugar present, giving in comparison with.the
nitrogen the low ratio of 0.27. This was one of the earliest observations we
had made that hyperglycemia is reduced as a rule well in advance of the
descent of glycosuria.
The result showed no perceptible difference between intravenous and
subcutaneous administration of the extracts. With Dog 2, however, on
the same day (June 23) there was a much slower effect from use of Extract
2B (1) subcutaneously than when it was given intravenously. This ex-
tract was prepared from fresh pig's pancreas by extraction in acidulated
alcohol after the manner described by Banting and Best (26), and probably
because the technique of preparation in this manner was still very new to
us it was not very potent-in fact, not so potent as the wholly unconcen-
trated extract (No. 21) of dog's pancreas, proportionally much smaller in
weight, used with Dog 1. Intravenous administration of 25 cc. lowered
the blood sugar in 21 hours from 0.384 to 0.258 and a second dose of 20 cc.
given subcutaneously brought it down only a little farther in 4 hours more.
There was a more rapid descent of the D:N ratio. Starting at 2.82 at
1 p.m., it fell to 0.96 at 3 p.m. and 0.35 at 4.40 p.m. The night urine, how-
ever, showed a complete return to the condition of total diabetes. Whether
this difference in the behavior of Dogs 1 and 2 was due to individuality of
reaction or to difference in the mode of extraction was not then, and is not
yet, entirely clear.
On June 24, 200 cc. of Perfusate 17 (Paper II on perfusates (27)) were given
after neutralization by stomach tube to Dog 1 and on the same day Dog 2
received in the same manner 38 cc. of the first extract of dog's pancreas,
No. 21 (1). Neither of the preparations given in this manner proved very
effective. That given to Dog 2 reduced the blood sugar not more than
60 mg. and in this case there was no material reduction of the D:N ratio.
On June 25 no treatment was given to either dog. On June 26 at 11 a.m.
both animals were given suboutaneously an injection of acid extract made
exactly neutral to litmus. Extract 24 given to Dog 1 was made from two
dogs' pancreases. No. 25, given to Dog 2, was made from 1,000 gm. of fresh
pig's pancreas trimmed free of fat as nearly as possible. The former had
TH JOURBNAl O5 BIOLOGICAL ]BI55IT1, VOt. LYV, NO. 1