Korean J Physiol Pharmacol.  2015 May;19(3):197-202. 10.4196/kjpp.2015.19.3.197.

Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

• Sharma N
• Sim YB
• Park SH
• Lim SM
• Kim SS
• Jung JS
• Hong JS
• Suh HW

• KMID: 1791419
• DOI: http://doi.org/10.4196/kjpp.2015.19.3.197

Abstract

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 microg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Keyword

Blood glucose; Brain; Immobilization stress; Sulfonylurea

MeSH Terms

Animals
Blood Glucose*
Brain
Corticosterone
Glipizide
Glyburide
Immobilization*
Insulin
Mice
Mice, Inbred ICR
Plasma
Tolazamide
Blood Glucose
Corticosterone
Glipizide
Glyburide
Insulin
Tolazamide

Figure

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  Fig. 1 Effect of tolazamide, glyburide, glipizide or glimepiride administered intracerebroventricularly on the blood glucose level in immobilization stress model. Mice were pretreated i.c.v. with 30 µg of tolazamide, glyburide, glipizide or glimepiride for 10 min. Then mice were enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured at 30, 60 and 120 min after immobilization stress initiated, as shown in Fig. 1A, B, C and D respectively. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. (A: +++p<0.001, ++p<0.01; compared to PEC+IMO, B: +++p<0.001; B: *p<0.05; compared to PEC, ++p<0.01 compared to PEC+IMO, +p<0.05; compared to PEC+IMO; C: **p<0.01,*p<0.05; compared to PEC, +++p<0.001 compared to PEC+IMO; D: A: *p<0.05; compared to PEC, +++p< 0.001 compared to PEC+IMO). The number of animals used in the present study was 7~8 for each group.

• 

  Fig. 2 Effect of tolazamide administered intracerebroventricularly plasma corticosterone and insulin levels in immobilization stress model. Mice were pretreated i.c.v. with 30 µg of tolazamide for 10 min. Then mice were enforced into immobilization stress for 30 min and returned to the cage. The blood was collected from tailvein. (A) Plasma corticosterone and (B) insulin levels were measured 30 min after immobilization stress initiated. The vertical bars indicate the standard error of mean (A: ++p<0.01 tolazamide compared to tolazamide+IMO, B: ***p<0.001; compared to PEC+ IMO). The number of animals used in the present study was 7~8 for each group.

• 

  Fig. 3 Effect of glyburide administered intracerebroventricularly on the plasma corticosterone and insulin levels in immobilization stress model. Mice were pretreated i.c.v. with 30 µg of glyburide for 10 min. Then mice were enforced into immobilization stress for 30 min and returned to the cage. The blood was collected from tail-vein. (A) Plasma corticosterone and (B) insulin levels were measured 30 min after immobilization stress initiated. The vertical bars indicate the standard error of mean (A: +p<0.05; glyburide compared to glyburide+IMO, *p<0.05; compared to PEC+PBS, +++p<0.001, ++p< 0.01, +p<0.05; B: ***p<0.001; PEC and PEC IMO compared to glyburide and glyburide+IMO, respectively). The number of animals used in the present study was 7~8 for each group.

• 

  Fig. 4 Effect of glipizide administered intracerebroventricularly on the plasma corticosterone and insulin levels in immobilization stress model. Mice were pretreated i.c.v. with 30 µg of glipizide for 10 min. Then mice were enforced into immobilization stress for 30 min and returned to the cage. The blood was collected from tail-vein. (A) Plasma corticosterone and (B) insulin levels were measured 30 min after immobilization stress initiated. The vertical bars indicate the standard error of mean (A: ++p<0.01 glyburide compared to glyburide+IMO, B: *p<0.05; PEC and PEC+IMO compared to glyburide and glyburide+IMO, respectively). The number of animals used in the present study was 7~8 for each group.

• 

  Fig. 5 Effect of glimepiride administered intracerebroventricularly on the plasma corticosterone and insulin levels in immobilization stress model. Mice were pretreated i.c.v. 30 µg of glimepiride for 10 min. Then mice were enforced into immobilization stress for 30 min and returned to the cage. The blood was collected from tail-vein. (A) Plasma corticosterone and (B) insulin levels were measured 30 min after immobilization stress initiated. The vertical bars indicate the standard error of mean. (A: +++p<0.001; glimepiride compared to glimepiride+IMO, *p<0.05; PEC and PEC+IMO compared to glimepiride and glimepiride +IMO respectively, B: ***p<0.001; PEC compare to glimepiride). The number of animals used in the present study was 7~8 for each group.

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