Tolbutamide (HLS 831) is a sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE.

cAMP stimulated protein kinase:4 mM

连续七天每天450 mg/kg Tolbutamide处理细胞,能够明显增加胰岛素和脂肪细胞的结合.结合曲线反映了受体位点数量的增加而非它们的亲和力增加.这种效应与对脂肪组织中胰岛素增强应答相关.与对照组相比,在有胰岛素存在时,用Tolbutamide处理的动物脂肪细胞能够明显地将更多的葡萄糖转化成脂肪.小的剂量下Tolbutamide能够通过刺激胰岛素的分泌产生代谢效应,但这种剂量不能提供更多的胰岛素结合位点.胰岛素结合位点的增加仅在大剂量的Tolbutamide存在时出现,但这种剂量下,会减少胰岛素的整体水平,包括胰腺的分泌和血清中胰岛素的水平.

Tolbutamide只能帮助机体正常产生胰岛素的这类病人来降低血糖。Tolbutamide能同时抑制基底蛋白激酶和环腺苷酸激活的蛋白激酶活性,IC50浓度为4 mM。Tolbutamide能够剂量依赖地抑制胰高血糖素诱导的双功能蛋白的磷酸化。在储存10（-9）M 胰高血糖素的情况下,加入2 mM Tolbutamide能够降低6磷酸果糖激酶的活性并增加果糖2,6二磷酸酯酶的活性。Tolbutamide还能够抑制犬类心脏中游离以及膜结合蛋白酶的活性。对脂肪组织的环腺苷酸依赖蛋白激酶活性的抑制作用可能是Tolbutamide抗脂解作用的原因。Tolbutamide还能够通过增加Cx43的浓度来抑制C6胶质细胞的增殖,Cx 43的浓度与Cdk激酶的抑制因子p21和p27上调所引起的pRb磷酸化降低相关。

cAMP kinase assay: Diced epididymal fat pads from fed Wistar rats (175-225 gm) are obtained after decapitation and incubated at 37 °C for two hours in Krebs-bicarbonate buffer containing 1.27 mM CaCl2. When added, Tolbutamide is present only during the incubation. After incubation fat pads are rinsed and sonicated in cold Krebs-bicarbonate buffer. The aqueous supematants from centrifugation at 50,000 × g for 30 minutes at 4 °C contained 0.75 to 1.25 mg protein per mL and are assayed for cyclic AMP-stimulated protein kinase activity. The assay is performed in 0.2 mL with these additions, 10 μmoles sodium glycerofiosphate pH 7.0, 2 μmoles sodium fluoride, 0.4 μmoles theophylline, 0.1 μmoles ethylene glyool bis (β-aminoethyl ether)-N, N'-tetraaoetic acid, 3 μmoles magnesium chloride, 0.3 mg mixed histone, 2 nmoles (γ- 32P) ATP, 1 nmoles cyclic AMP when indicated, and 0.05 ml of supernatant.

C6 glioma cells are incubated in serum-free DMEM at 37 °C for at least 24 hours before each experiment. Tolbutamide (400 μM) is incubated for 24 hours in serum-free medium. Incubations are performed at 37 °C in an atmosphere of 95% air/5% CO2 with 90–95% humidity. (Only for Reference)