Effects of the Serotonergic Anxiolytic Buspirone on Plasma Glucose and Glucose-Induced Hyperglycemia in Mice

Sugimoto, Yukihiko; Takashima, Nozomu; Noma, Toshiko; Yamada, Jun

doi:10.1254/jphs.93.446

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…17) We demonstrated that 1-PP increased serum insulin levels and facilitates glucose-induced insulin release. 12) In the present study, 1-PP increased serum insulin levels in both non-stressed and stressed mice, similar to the results with buspirone. Therefore, it is suggested that 1-PP formed from buspirone plays a role in inhibitory effects of stress-induced hyperglycemia following the administration of buspirone.…”

Section: Fig 3 Effects Of 1-pp On Plasma Glucose and Serum Insulin supporting

confidence: 90%

“…12) Flesinoxan, another 5-HT 1A receptor agonist did not affect glucose levels in mice either, although it was reported that it induced hyperglycemia in rats. 15,16) Thus, there is a difference in glycemic responses to 5-HT 1A receptor agonists between mice and rats.…”

Section: Discussionmentioning

confidence: 96%

“…12) This suggests that inhibitory effects of buspirone on stress-induced hyperglycemia may be mediated by insulin. Thus, we examined the effects of buspirone on serum insulin levels in stressed mice.…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory Effects of the 5-HT1A Receptor Agonist Buspirone on Stress-Induced Hyperglycemia in Mice: Involvement of Insulin and a Buspirone Metabolite, 1-(2-Pyrimidinyl)piperazine (1-PP)

Sugimoto

Takashima

Noma

et al. 2005

Biological & Pharmaceutical Bulletin

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Benzodiazepine derivatives are widely used for anxiety, by the facilitation of GABA neurotransmission. It is well known that serotonin (5-HT) is involved in several neurological functions.1) The 5-HT 1A receptor is related to emotion and the 5-HT 1A receptor agonists induce anxiolytic and antidepressant effects in humans and animals. 2,3) Buspirone is known to be a 5-HT 1A receptor agonist and is used to treat anxiety.2) Stress induces several neuroendocrinological effects such as activation of the hypothalamus-pituitary-adrenal (HPA) axis and elicits activation of sympathetic tone. 4,5) Hyperglycemic responses to stress are recognized as an index of the sympathetic nervous system. 4) Stress induces changes in emotion and mood. 5) Recently, it was reported that the 5-HT 1A receptor agonist might be effective for stress-induced behavioral depressant symptoms. 2)Previous reports demonstrated that 5-HT receptor is involved in glucose regulation. The 5-HT 1A receptor agonist 8-OH-DPAT elicits hyperglycemia in rats and mice.6,7) The 5-HT 1A receptor partial agonist buspirone and ipsapirone elevate the glucose levels of rats. 8,9) These effects of 5-HT 1A receptor agonists are considered due to facilitating adrenaline release from the adrenal medulla.10,11) However, there may be species differences in the effects of buspirone on glucose levels between rats and mice. We previously reported that buspirone did not elevate glucose levels of mice and it increases serum insulin levels.12) In addition, buspirone reduces glucose-induced hyperglycemia in mice by increasing insulin levels. 12)It is well known that stress elicits hyperglycemia and stress-induced hyperglycemia may be a factor in contributing to diabetes. 4,13) Since buspirone is available in stressed-patients with accompanying with anxiety, the possibility that buspirone may also suppress stress-induced hyperglycemia is postulated. However, it is not clear whether buspirone modifies stress-elevated hyperglycemia. In this paper, we examined the effects of buspirone on stress-induced hyperglycemia and involvement of insulin in the effects of buspirone. MATERIALS AND METHODS AnimalsMale ddY mice weighing 28-32 g were obtained from SLC Japan Inc (Japan). Mice were fed with free access to food and water and they were housed under a controlled 12-h/12-h light-dark cycle (light from 7:00 a.m. to 7:00 p.m.), with room temperature at 23Ϯ1°C and humidity at 55Ϯ5%. For experiments with glucose, mice were fasted for 20 h. The experimental procedure was approved by the Kobe Pharmaceutical University Animal Care and Use Committee.Drug Treatment Buspirone HCl, 1-(2-pyrimidinyl)-piperazine (1-PP) HCl were obtained from Sigma (U.S.A.). Drugs were dissolved in saline. Buspirone and 1-PP were injected s.c. 30 min before immobilization stress.Immobilization and Determination of Plasma Glucose and Insulin Levels Mice were restrained by placing in individual wire cages (3.5 cmϫ8.3 cmϫ2.3 cm). After immobilization for 15, 30, 60 and 120 min, mice were immediately decapitated and blood ...

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Section: Fig 3 Effects Of 1-pp On Plasma Glucose and Serum Insulin supporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

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Inhibitory Effects of the 5-HT1A Receptor Agonist Buspirone on Stress-Induced Hyperglycemia in Mice: Involvement of Insulin and a Buspirone Metabolite, 1-(2-Pyrimidinyl)piperazine (1-PP)

Sugimoto

Takashima

Noma

et al. 2005

Biological & Pharmaceutical Bulletin

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“…Both inhibition and stimulation of insulin secretion have been observed with serotonergic agonists (21,22). Interestingly, the selective serotonin reuptake inhibitor fluoxetine improved insulin sensitivity in obese humans (23), and the serotonergic anxiolytic buspirone reduced glucose-induced hyperglycemia in mice (24). On the other hand, increased noradrenergic effects may be important, as catecholamines can promote hyperglycemia through multiple mechanisms (e.g., inhibition of insulin secretion, stimulation of gluconeogenesis, decrease in insulin sensitivity) (25,26).…”

Section: Relationships Between Pain and Metabolic Parametersmentioning

confidence: 99%

Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?

et al. 2007

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OBJECTIVE -We examined changes in metabolic parameters in clinical trials of duloxetine for diabetic peripheral neuropathic pain (DPNP).RESEARCH DESIGN AND METHODS -Data were pooled from three similarly designed clinical trials. Adults with diabetes and DPNP (n ϭ 1,024) were randomized to 60 mg duloxetine q.d., 60 mg b.i.d., or placebo for 12 weeks. Subjects (n ϭ 867) were re-randomized to 60 mg duloxetine b.i.d. or routine care for an additional 52 weeks. Mean changes in plasma glucose, lipids, and weight were evaluated. Regression and subgroup analyses were used to identify relationships between metabolic measures and demographic, clinical, and electrophysiological parameters.RESULTS -Duloxetine treatment resulted in modest increases in fasting plasma glucose in short-and long-term studies (0.50 and 0.67 mmol/l, respectively). A1C did not increase in placebo-controlled studies; however, a greater increase was seen relative to routine care in long-term studies (0.52 vs. 0.19%). Short-term duloxetine treatment resulted in mean weight loss (Ϫ1.03 kg; P Ͻ 0.001 vs. placebo), whereas slight, nonsignificant weight gain was seen in both duloxetine and routine care groups with longer treatment. Between-group differences were seen for some lipid parameters, but these changes were generally small. Metabolic changes did not appear to impact improvement in pain severity seen with duloxetine, and nerve conduction was also not significantly impacted by treatment.CONCLUSIONS -Duloxetine treatment was associated with modest changes in glycemia in patients with DPNP. Other metabolic changes were limited and of uncertain significance. These changes did not impact the significant improvement in pain observed with duloxetine treatment. Diabetes Care 30:21-26, 2007N europathy is the most common diabetic microvascular complication, affecting up to 50% of all individuals with diabetes (1). Substantial morbidity is associated with diabetic peripheral neuropathy (DPN), which is the leading risk factor for diabetic foot complications and nontraumatic amputations. Though these late complications frequently occur in the insensate foot, symptomatic DPN also significantly impacts quality of life (2,3). Estimates of the prevalence of diabetic peripheral neuropathic pain (DPNP) vary from 3% to Ͼ20% (4).For many agents, the data supporting effectiveness is limited. In addition, nearly all treatments are associated with safety or tolerability issues. One category of side effects common to a number of the antidepressant and anticonvulsant drugs is related to metabolic changes. Weight gain is seen with tricyclic antidepressants (TCAs) (5) and anticonvulsants (e.g., valproate, gabapentin, pregabalin) (6). Changes in plasma glucose have also been reported with TCAs (7,8) and phenytoin (9), and dyslipidemia can be seen with carbamazepine (10).Duloxetine has demonstrated efficacy in several large clinical trials of DPNP (11-13) and is one of only two drugs to have received regulatory approval for the treatment of this condition. As a selective reupt...

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“…Insulin levels decreased, blood glucose levels improved, and HOMA-IR index values decreased in our treatment groups, although the values in the BUS 5 and combined treatment groups were lower than in the other groups. There are a number of studies evaluating the effect of buspirone on glycemic status in the literature [26,27]. Buspirone decreased blood glucose levels in all studies, although its effects on insulin levels varied.…”

Section: Discussionmentioning

confidence: 99%

An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

Çavuşoğlu

Darıverenli

Vural

et al. 2020

Turkish Journal of Biochemistry

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AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

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Effects of the Serotonergic Anxiolytic Buspirone on Plasma Glucose and Glucose-Induced Hyperglycemia in Mice

Cited by 5 publications

References 21 publications

Inhibitory Effects of the 5-HT1A Receptor Agonist Buspirone on Stress-Induced Hyperglycemia in Mice: Involvement of Insulin and a Buspirone Metabolite, 1-(2-Pyrimidinyl)piperazine (1-PP)

Inhibitory Effects of the 5-HT1A Receptor Agonist Buspirone on Stress-Induced Hyperglycemia in Mice: Involvement of Insulin and a Buspirone Metabolite, 1-(2-Pyrimidinyl)piperazine (1-PP)

Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?

An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

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