Disappearance of glibenclamide-induced hypoglycemia in Wistar-Kyoto rats.
The aim of the present study is to investigate difference in sensitivity to glibenclamide, a sulfonylurea oral antidiabetic agent, among Wistar rats, Spontaneously Hypertensive rats (SHR/Izm) and Wistar-Kyoto rats (WKY/Izm). We examined the effect of glibenclamide on blood levels of glucose and insulin in these rat strains. Under anesthesia with pentobarbital sodium (50 mg/kg, i.p.), blood samples were collected before and 5-120 min after administration of glibenclamide (10 mg/kg, i.p.). Blood levels of glucose and insulin in each sample were measured by glucose oxidase method and radioimmunoassay, respectively. In 8 week-old rats of all strains tested, blood levels of glucose were decreased by glibenclamide. In 12-20-week-old rats, although blood levels of glucose in Wistar and SHR/Izm were decreased after glibenclamide administration, those of WKY/Izm were not decreased. In rats of this age, time-course and extent of increases in blood insulin levels observed after administration of glibenclamide in WKY/Izm was almost the same as that of SHR/Izm, however, smaller than that of Wistar. Both insulin secretions induced via inactivation of ATP-sensitive K+ channel and sensitivity of pancreatic beta-cells to insulin seems to be decreased in WKY/Izm after 12 weeks of age. This phenomenon may explain the mechanism of glucose intolerance previously reported in WKY/Izm.
Sakamoto
Kenji
K
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan. sakamotok@pharm.kitasato-u.ac.jp
Yonoki
Yuzuru
Y
Fujioka
Takamitsu
T
Matsumura
Mizuho
M
Mitsuta
Yoko
Y
Sano
Misako
M
Saito
Maki
M
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000375:Aging / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005949:Glucose Oxidase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005949:Glucose Oxidase; D005905:Glyburide