Disopyramide induces insulin secretion and plasma glucose diminution: studies using the in situ canine pancreas.
The mechanism of disopyramide-induced hypoglycemia, a life-threatening complication in the antiarrhythmic drug treatment, is still controversial. To elucidate this, we have evaluated plasma insulin (IRI) and glucagon (IRG) responses in the pancreatic vein (PV) of the in situ pancreas as well as responses of plasma IRI, IRG, and glucose in the femoral artery (FA) to disopyramide phosphate administration in anesthetized dogs. First, infusion of disopyramide at a dose of 50 mg for ten minutes directly into the pancreatic artery, but not the vehicle, increased significantly plasma IRI concentration in the PV (P less than .05 or less), where the IRI response started within three minutes and reached a peak of 2.8-fold preinfusion value at 30 minutes after starting the infusion (n = 7). Plasma IRI concentration in the FA also increased slightly but significantly (P less than .05). Plasma IRG concentration in the PV initially decreased significantly (P less than .05 or less) and in the FA at one point (P less than .05) during the infusion, and then increased significantly after cessation of the infusion, showing a peak of 1.9-fold preinfusion value at 60 minutes in the PV and the FA (P less than .05). Plasma glucose concentration in the FA decreased slowly and significantly after the infusion (P less than .05 or less) and fell by 16% of the baseline value at 60 minutes (P less than .05). Second, serum disopyramide concentration of 13.7 +/- 2.8 micrograms/mL at ten minutes, which corresponds to a twofold to threefold concentration of the human therapeutic level (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Nakabayashi
H
H
Department of Internal Medicine (II), School of Medicine, Kanazawa University, Japan.
Ito
T
T
Igawa
T
T
Hiraiwa
Y
Y
Imamura
T
T
Seta
T
T
Kawato
M
M
Usukura
N
N
Takeda
R
R
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D004206:Disopyramide