Activation of spinal α2 adrenergic receptors induces hyperglycemia in mouse though activating sympathetic outflow

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung‐Su; Lim, Seungyup; Jung, Jun‐Sub; Suh, Hwal

doi:10.1016/j.ejphar.2014.08.022

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…The activation of spinal α 2 -adrenergic receptors exerts several pharmacological profiles such as hypotension, hypothermia, hypnosis, analgesia and sedation [ 18 19 20 21 22 23 ]. We recently found that the activation of α 2 -adrenergic receptors located in the spinal cord elevates the blood glucose level [ 24 ]. However, the role of spinal α 2 -adrenergic receptor activation in sepsis-induced mortality has not been characterized yet.…”

Section: Introductionmentioning

confidence: 99%

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Kim

Park

Lee

et al. 2017

Korean J Physiol Pharmacol

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The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

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Section: Introductionmentioning

confidence: 99%

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Kim

Park

Lee

et al. 2017

Korean J Physiol Pharmacol

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“…Tamsulosin, an α 1 antagonist, could improve insulin resistance [22]. Inhibition of postsynaptic α 2 ‐adrenoceptors in the pancreatic beta‐cell membrane could decrease blood glucose levels [23]. Notably, PPAR‐γ agonists can improve insulin sensitivity and glycemic control in T2DM [24].…”

Section: Discussionmentioning

confidence: 99%

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

Shen

Lin

Yen

et al. 2017

The Kaohsiung J of Med Scie

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This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

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“…pretreatment with PTX also dose-dependently attenuated the blood glucose level induced by baclofen [42]. Furthermore, it has been reported that hyperglycemia induced by clonidine, an α2-adrenergic receptor agonist, is blocked by PTX pretreated spinally, suggesting that the activation of PTX-sensitive inhibitory G-proteins by clonidine may cause hyperglycemia [43]. In the present study, the blockade of hyperglycemia induced by physical and emotional stresses by PTX pretreated supraspinally or spinally suggests that the activation of the PTX-sensitive G-proteins may be one of the mechanisms involved in stress-induced hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

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

Suh

Sim

Park

et al. 2016

Korean J Physiol Pharmacol

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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.

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Activation of spinal α2 adrenergic receptors induces hyperglycemia in mouse though activating sympathetic outflow

Cited by 8 publications

References 39 publications

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

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

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Activation of spinal α2 adrenergic receptors induces hyperglycemia in mouse though activating sympathetic outflow

Cited by 8 publications

References 39 publications

The activation of α2-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

The activation of α2-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

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

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The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality