KU14R

KU14R, an imidazole analog of efaroxan, is a putative imidazoline I3 receptor antagonist and reversible K_ATP channel inhibitor. KU14R inhibits K_ATP channel activity in mouse pancreatic β cells with an IC₅₀ of 31.9 μmol/L, and also suppresses Kir6.2 ΔC26 channel activity. KU14R exerts model-dependent antagonistic effects on imidazoline-sensitive insulin secretion. KU14R can be used in the research of diabetes-related diseases^{[1][2][3][4][5]}.
In Vitro:KU14R (300 μM; doses to determine IC₅₀) potently blocks K_ATP channels in primary mouse pancreatic β cells, with an IC₅₀ of 31.9 μM, and achieves nearly complete inhibition at 300 μM^[1].
KU14R (100 μM) inhibits the Kir6.2 ΔC26 channel expressed in HEK cells, reducing channel activity to 45.2% of that in the control group at 100 μM^[1].
KU14R (100 μM) depolarizes the membrane potential of mouse pancreatic β cells to -33.4 mV, and fails to repolarize cells that have been depolarized by efaroxan^[1].
KU14R (100 μM; 30 min) does not alter cAMP levels in rat islets, nor does it reduce the forskolin (5 μM)- or IBMX (50 μM)-induced elevation of cAMP, suggesting that the antagonistic effect of KU14R on cAMP-dependent enhancement of insulin secretion occurs downstream of cAMP generation^[4].
KU14R (10^-5 M and 10^-4 M; pre-incubated for 10 min) antagonizes the response of the α2-adrenoceptor agonist UK14304 in isolated mouse vas deferens functional assays, with K_i values of 4.44 × 10^-6 M and 4.14 × 10^-6 M, respectively; KU14R (10^-6-10^-5 M) does not alter the concentration-response curve of the imidazoline ligand S22068^[2].
KU14R (30-300 μM) barely potentiates glucose-induced insulin secretion in freshly isolated islets from NMRI mice; when glucose increases from 5 mmol/L to 10 mmol/L, the integrated insulin secretion in the presence of KU14R reaches 226% of the pre-stimulation level, and 100 μM KU14R does not antagonize efaroxan (100 μM)-induced insulin secretion^[1].
KU14R (0.1-1 μM; 7 mM glucose) dose-dependently reduces morin- or efaroxan-induced insulin secretion in MIN6 cells without altering basal insulin secretion; treatment with KU14R alone up to 50 μM also does not significantly change basal insulin secretion^[3].
KU14R (1 μM; 20 mM glucose) inhibits the further enhancing effect of morin (1 μM) on high glucose-induced insulin secretion, while KU14R alone does not reduce insulin secretion induced by 20 mM glucose^[3].
KU14R (100 μM; 1 h) does not alter basal insulin secretion induced by 6 or 20 mmol/L glucose in freshly isolated Wistar rat islets, but significantly inhibits the potentiating effects of efaroxan (100 μM), IBMX (50 μM) or forskolin (5 μM) on insulin secretion^[4].
KU14R itself does not alter insulin secretion from isolated islets of Wistar rats under 4-20 mM glucose conditions, but dose-dependently reverses the insulinotropic effect of efaroxan, exhibiting functional antagonism^[5].
KU14R (1-100 μM; 10 min) exhibits weak α₂-adrenoceptor antagonist activity in isolated mouse vas deferens. It significantly and competitively inhibits UK14304-induced twitch suppression at concentrations of 10 μM and 100 μM, and directly suppresses twitches at 100 μM^[2]. In Vivo:KU14R (4-25 mg/kg; i.p.; single dose) induces dose-dependent hypoglycemia in healthy male CBA/Ca mice, with an ED₅₀ of 16 mg/kg, and the response at 20 mg/kg involves increased plasma insulin levels^[2].
KU14R (16 mg/kg; i.p.; single dose) does not act as an antagonist of the hypoglycemic effect of S22068 (24 mg/kg) in healthy male CBA/Ca mice^[2].