Korean J Physiol Pharmacol.  2013 Dec;17(6):493-497. 10.4196/kjpp.2013.17.6.493.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

• Sim YB
• Park SH
• Kang YJ
• Kim SS
• Kim CH
• Kim SJ
• Lim SM
• Jung JS
• Ryu OH
• Choi MG
• Suh HW

• KMID: 2285475
• DOI: http://doi.org/10.4196/kjpp.2013.17.6.493

Abstract

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 microg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

Keyword

Blood glucose; Glinides; Spinal; Streptozotocin; Supraspinal

MeSH Terms

Animals
Blood Glucose
Brain
Carbamates
Central Nervous System
Cyclohexanes
Glucose*
Hand
Insulin
Mice*
Mice, Inbred ICR
Phenylalanine
Piperidines
Plasma
Spinal Cord
Streptozocin
Blood Glucose
Carbamates
Cyclohexanes
Glucose
Insulin
Phenylalanine
Piperidines
Streptozocin

Figure

• 

  Fig. 1 Effects of repaglinide administered i.c.v. or i.t. on the blood glucose level in D-glucose-fed model. Mice were pretreated i.c.v. (A) and i.t. (B) with 5, 20 or 30 µg of repaglinide for 10 min. Then 2 g/kg of D-glucose were orally fed. The blood glucose level was measured at 30, 60 and 120 min after D-glucose administration. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (**p<0.01, ***p<0.005; compared to D-Glucose+PEC group). The number of animal used in each group was 8~10.

• 

  Fig. 2 Effects of nateglinide administered i.c.v. or i.t. on the blood glucose level in D-glucose-fed model. Mice were pretreated i.c.v. (A) and i.t. (B) with 5, 20 or 30 µg of repaglinide or nateglinide for 10 min. Then 2 g/kg of D-glucose were orally fed. The blood glucose level was measured at 30, 60 and 120 min after D-glucose administration. The blood was collected from tail-vein. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test. The number of animal used in each group was 8~10.

• 

  Fig. 3 Effects of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model. Mice were pretreated intraperitoneally with STZ (150 mg/kg) for 6 days. And then, 5, 20 or 30 µg/5 µl of repaglinide was administered treated i.c.v. (A) or i.t. (B) The blood glucose level was measured at 30, 60 and 120 min after repaglinide injection. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (*p<0.05, **p<0.01; compared to STZ+PEC group). The number of animal used in each group was 8~10.

• 

  Fig. 4 Effects of repaglinide and nateglinide administered i.c.v. or i.t. on the plasma insulin level in D-glucose-fed and STZ-treated models. Mice were pretreated i.c.v. (A) and i.t. (B) with 30 µg of repaglinide and nateglinide for 10 min. Then 2 g/kg of D-glucose were orally fed. The plasma insulin level was measured at 30 min after D-glucose administration. In another experiment, mice were pretreated intraperitoneally with STZ (150 mg/kg) for 6 days. And then, 30 µg/5 µl of repaglinide and nateglinide was administered treated i.c.v. (C) or i.t. (D) The plasma insulin level was measured at 30 min after repaglinide and nateglinide injection. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test. The number of animal used in each group was 6~8.

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