Effect of KAD-1229, a nonsulfonylurea hypoglycemic agent, on plasma glucose and insulin in streptozotocin-induced diabetic dogs.
Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.
Misawa
K
K
Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., Hotaka, Nagano, Japan. keiko_misawa@pharm.kissei.co.jp
Ichikawa
K
K
Ojima
K
K
Hamano
S
S
Kitamura
T
T
Komatsu
H
H
D000818:Animals; D000900:Anti-Bacterial Agents; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004195:Disease Models, Animal; D004285:Dogs; D005907:Gliclazide / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D054833:Isoindoles; D008297:Male; D013311:Streptozocin
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D054833:Isoindoles; D013311:Streptozocin; C087255:mitiglinide; D005907:Gliclazide