Chlorpropamide

Chlorpropamide acts through a cyclic AMP-independent mechanism. The addition of 0.2 mM Chlorpropamide to hepatocytes isolated from fed rats, raises the cellular concentration of fructose-2,6-bisphosphate (F-2, 6-P₂). The accumulation of F-2, 6-P₂ caused by Chlorpropamide (1 mM) is parallel to the stimulation of L-lactate production (36.6 versus 26.1 μmol of lactate/g of cells) and to the inhibition of gluconeogenesis (0.57 versus 0.94 μmol of [U-¹⁴C]pyruvate converted to glucose/g of cells). Chlorpropamide enhances the inhibitory action evoked by insulin on glucagon-stimulated gluconeogenesis^[1]. Chlorpropamide treatment has no effect on insulin binding, altering neither receptor number nor affinity in rat adipocytes. Chlorpropamide (175 μg/mL) enhances 2-deoxyglucose transport in both the absence (17%) and presence (20%) of insulin. Chlorpropamide significantly increases glucose metabolism and total lipids in both the absence (30%) and presence (31%) of insulin^[2]. Chlorpropamide competitively inhibits antidiuretic hormone (ADH) binding and adenylyl cyclase (AC) stimulation with K_i of 2.8 mM and 250 μM, respectively, in the LLC-PK1 cell line. Chlorpropamide (333 μM) increases the apparent K_a of ADH for AC activation (0.31 vs. 0.08 nM) without affecting a maximal response. Twenty-four-hour Chlorpropamide exposure (100 μM) upregulates the ADH receptors without affecting affinity, which lowers K_a and increases basal AC activity and maximal response (1.86 vs. 1.35 and 14.9 vs. 10.6 fmol cAMP/min/1000 cells).