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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 b b-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.

β 1 -and β 2 -Adrenergic receptors (β 1 -AR and β 2 -AR) are co-expressed in numerous tissues, for example, heart and bladder. They play a very important role in the responses of a variety of organs to sympathetic nerve stimulation. Recent studies suggest that many G protein-coupled receptors, such as β 1 -AR, β 2 -AR, μ opioid receptor and δ opioid receptor, can form homo-and heterooligomers. Previous studies demonstrated that the β 1 -AR and β 2 -AR formed dimers in living HEK 293 cells. The aim of the present study is to investigate whether such heterooligomerization affect the agonist-induced receptor internalization in the CHO-K1 cells stably co-expressing β 1 -AR and β 2 -AR. Using co-immunoprecipitation, we confirmed that β 1 -AR and β 2 -AR formed heterooligomers in the CHO-K1 cells. In cells co-expressing β 1 -AR and β 2 -AR, 30% of β 1 -AR was internalized by isoproterenol, whereas only 20% of β 1 -AR was internalized in cells expressing the β 1 -AR alone. Heterooligomerization did not affect the ratio of internalized β 2 -AR. Salmeterol, a specific β 2 -AR agonist, broke β 1 -AR/β 2 -AR heterooligomers, and induced β 2 -AR-specific internalization in cells co-expressing β 1 -AR and β 2 -AR. The present study demonstrated that heterooligomerization between β 1 -AR and β 2 -AR accelerates the isoproterenol-promoted internalization of the β 1 -AR, and that salmeterol induces β 2 -AR-specific internalization in Chinese hamster ovary (CHO) cells stably co-expressing β 1 -AR and β 2 -AR.