Korean J Physiol Pharmacol.  2016 Sep;20(5):467-476. 10.4196/kjpp.2016.20.5.467.

Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress

• Suh HW
• Sim YB
• Park SH
• Sharma N
• Im HJ
• Hong JS

• KMID: 2350503
• DOI: http://doi.org/10.4196/kjpp.2016.20.5.467

Abstract

In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism.

Keyword

Blood glucose; Cold-water swimming stress; Emotional stress-Physical stress; Pertussis toxin-sensitive G proteins; Restraint stress

MeSH Terms

Animals
Blood Glucose*
Corticosterone
GTP-Binding Proteins
Hyperglycemia
Hypoglycemia
Insulin
Mice
Pertussis Toxin*
Plasma
Stress, Psychological
Swimming
Up-Regulation
Whooping Cough*
Blood Glucose
Corticosterone
GTP-Binding Proteins
Insulin
Pertussis Toxin

Figure

• 

  Fig. 1 Effect of PTX pretreated i.c.v. on blood glucose level induced by an electric foot-shock physical stress.An electrical foot shock was applied to mice 10 stimuli/10 min/1 day. The mice were pretreated i.c.v. once with PTX (0.05 or 0.1 µg) for 6 days before a stimulation of electrical foot-shock physical stress. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation. The 0 time point is basal level before drug treated mice (n=8 per group; **p<0.01, compared to vehicle group (basal time), +p<0.05, ++p<0.01, +++p<0.001, compared to vehicle group). The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; ***p<0.001, compared to saline group; ++p<0.01, +++p<0.001, compared to saline+physical stress group). The bars indicate the means±SEM.

• 

  Fig. 2 Effect of PTX pretreated i.t. on blood glucose level induced by an electric foot-shock physical stress.An electrical foot shock was applied to mice 10 stimuli/10 min/1 day. The mice were pretreated i.t. once with PTX (0.05 or 0.1 µg) for 6 days before a stimulation of electrical foot-shock physical stress. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation (n=8 per group; *p<0.05, **p<0.01, compared to vehicle group (basal time), +p<0.05, ++p<0.01, compared to vehicle group). The 0 time point is basal level before drug treated mice. The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; **p<0.01, ***p<0.001, compared to saline group; ++p<0.01, +++p<0.001, compared to saline+physical stress group). The bars indicate the means±SEM.

• 

  Fig. 3 Effect of PTX pretreated i.c.v. on blood glucose level induced by emotion stress.After the mice were pretreated i.c.v. once with PTX (0.05 or 0.1 µg) for 6 days, emotional stress group witnessed a group of mice that an electrical foot shock was applied with 10 stimuli/10 min/1 day. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation (n=8 per group; ***p<0.001compared to vehicle group (basal time); +p<0.05, ++p<0.01, +++p<0.001, compared to vehicle group). The 0 time point is basal level before drug treated mice. The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; **p<0.01, ***p<0.001, compared to saline group; ++p<0.01, +++p<0.001, compared to saline+emotional stress group). The bars indicate the means±SEM.

• 

  Fig. 4 Effect of PTX pretreated i.t. on blood glucose level induced by emotion stress.After the mice were pretreated i.t. once with PTX (0.05 or 0.1 µg) for 6 days, emotional stress group witnessed a group of mice that an electrical foot shock was applied with 10 stimuli/10 min/1 day. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation (n=8 per group; **p<0.01, ***p<0.001, compared to vehicle group (basal time), ++p<0.01, +++p<0.001, compared to vehicle group). The 0 time point is basal level before drug treated mice. The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; ***p<0.001, compared to saline group; +p<0.05, +++p<0.001, compared to saline+emotional stress group). The bars indicate the means±SEM.

• 

  Fig. 5 Effect of PTX pretreated i.c.v. on blood glucose level induced by immobilization stress.After the i.c.v. pretreatment once with PTX (0.05 or 0.1 µg) for 6 days, mice were enforced into immobilization stress for 30 min and returned to the cage. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation. The 0 time point is basal level before drug treated mice (n=8 per group; *p<0.05, **p<0.01, ***p<0.001, compared to vehicle group (basal time), +p<0.05, ++p<0.01, +++p<0.001, compared to vehicle group). The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; **p<0.01, ***p<0.001, compared to saline group; ++p<0.01, +++p<0.001, compared to saline+immobilization stress group).The bars indicate the means±SEM.

• 

  Fig. 6 Effect of PTX pretreated i.t. on blood glucose level induced by immobilization stress.After the i.t. pretreatment once with PTX (0.05 or 0.1 µg) for 6 days, mice were enforced into immobilization stressfor 30 min and returned to the cage. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation. The 0 time point is basal level before drug treated mice (n=8 per group; **p<0.01, ***p<0.001, compared to vehicle group (basal time), +p<0.05, ++p<0.01, +++p<0.001, compared to vehicle group). The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; **p<0.01, ***p<0.001, compared to saline group; ++p<0.01, +++p<0.001, compared to saline+immobilization stress group). The bars indicate the means±SEM.

• 

  Fig. 7 Effect of PTX pretreated i.c.v. on blood glucose level induced by the cold-water swimming stress.After the i.c.v. pretreatment once with PTX (0.05 or 0.1 µg) for 6 days, mice were enforced into swimming at cold water (at 4℃) for 3 min and returned to the cage. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation. The 0 time point is basal level before drug treated mice (n=8 per group; *p<0.05, ***p<0.001, compared to vehicle group (basal time), +p<0.05, ++p<0.01, +++p<0.001, compared to vehicle group). The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; *p<0.05, ***p<0.001, compared to saline group; +p<0.05, ++p<0.01, +++p<0.001, compared to saline+cold-swimming stress group). The bars indicate the means±SEM.

• 

  Fig. 8 Effect of PTX pretreated i.t. on blood glucose level induced by the cold-water swimming stress.After the i.t. pretreatment once with PTX (0.05 or 0.1 µg) for 6 days, mice were enforced into swimming at cold water (at 4℃) for 3 min and returned to the cage. The blood glucose (A) level was measured at 30, 60 and 120 min after stress stimulation. The 0 time point is basal level before drug treated mice (n=8 per group; **p<0.01, compared to vehicle group (basal time), +p<0.05, ++p<0.01, compared to vehicle group). The plasma corticosterone (B) and insulin (C) levels were measured at 30 min after the stress stimulation (n=8 per group; *p<0.05, ***p<0.001, compared to saline group; +p<0.05, ++p<0.01, +++p<0.001, compared to saline+cold-swimming stress group. The bars indicate the means±SEM.

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