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Insulin modulates the strong reinforcing effects of nicotine and changes in insulin biomarkers in a rodent model of diabetes.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-01-07 , DOI: 10.1038/s41386-018-0306-3 Bryan Cruz 1 , Rodolfo J Flores 1 , Kevin P Uribe 1 , Evangelina J Espinoza 1 , Charles T Spencer 2 , Katherine M Serafine 1 , Arbi Nazarian 3 , Laura E O'Dell 1
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-01-07 , DOI: 10.1038/s41386-018-0306-3 Bryan Cruz 1 , Rodolfo J Flores 1 , Kevin P Uribe 1 , Evangelina J Espinoza 1 , Charles T Spencer 2 , Katherine M Serafine 1 , Arbi Nazarian 3 , Laura E O'Dell 1
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This study examined whether the strong reinforcing effects of nicotine and changes in insulin biomarkers observed in diabetic rats are modulated via insulin. A model of diabetes was employed involving administration of streptozotocin (STZ), which produces hypoinsulinemia in rats. The present study included vehicle- or STZ-treated rats that received sham surgery or insulin pellets. Two weeks later, the rats were given extended access to intravenous self-administration (IVSA) of saline or nicotine. Concomitant changes in food intake, water responses, and body weight were assessed during 12 days of IVSA. After the last session, plasma levels of insulin, leptin, amylin, and glucagon-like peptide-1 (GLP-1) were assessed using Luminex® technology. In a separate cohort, phosphorylated insulin receptor substrate-2 (pIRS-2) and insulin growth factor-1 receptor β (IGF-1Rβ) were assessed in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of vehicle- or STZ-treated rats that received sham surgery or an insulin pellet. STZ-treated rats displayed an increase in glucose levels, a decrease in body weight, and an increase in nicotine, food, and water intake relative to controls. STZ-treated rats also displayed a decrease in plasma insulin and leptin levels and an increase in amylin and GLP-1 levels relative to controls. Importantly, all of the STZ-induced changes in behavior and insulin biomarkers were prevented by insulin supplementation. STZ-treated rats also displayed a decrease in pIRS-2 and IGF-1Rβ in the NAc (but not VTA), an effect that was also prevented by insulin. These data suggest that insulin systems in the NAc modulate the strong reinforcing effects of nicotine in male diabetic rats.
中文翻译：
在糖尿病的啮齿动物模型中，胰岛素调节尼古丁的强力增强作用和胰岛素生物标志物的变化。
这项研究检查了在糖尿病大鼠中观察到的尼古丁的强效增强作用和胰岛素生物标志物的变化是否通过胰岛素调节。使用了一种糖尿病模型，其中涉及了链脲佐菌素（STZ）的施用，该链佐菌素会在大鼠中产生低胰岛素血症。本研究包括接受假手术或胰岛素颗粒治疗的经媒介物或STZ处理的大鼠。两周后，给予大鼠盐水或尼古丁的静脉自我给药（IVSA）的权限。在IVSA的12天内评估了食物摄入，水响应和体重的相应变化。在最后一次会议之后，使用Luminex®技术评估血浆中胰岛素，瘦素，胰岛淀粉样多肽和胰高血糖素样肽1（GLP-1）的水平。在一个单独的队列中，在接受了赋形剂或STZ治疗的大鼠的伏隔核（NAc）和腹侧被盖区（VTA）中评估了磷酸化的胰岛素受体底物2（pIRS-2）和胰岛素生长因子1受体β（IGF-1Rβ）。假手术或胰岛素沉淀。与对照组相比，经STZ处理的大鼠表现出葡萄糖水平的增加，体重的减少以及尼古丁，食物和水的摄入量的增加。与对照组相比，经STZ治疗的大鼠血浆胰岛素和瘦素水平降低，胰岛淀粉样多肽和GLP-1水平升高。重要的是，补充胰岛素可预防所有STZ诱导的行为变化和胰岛素生物标志物。经STZ处理的大鼠在NAc中也显示pIRS-2和IGF-1Rβ降低（但未显示VTA），胰岛素也可以阻止这种作用。
更新日期：2019-01-26
中文翻译：
在糖尿病的啮齿动物模型中，胰岛素调节尼古丁的强力增强作用和胰岛素生物标志物的变化。
这项研究检查了在糖尿病大鼠中观察到的尼古丁的强效增强作用和胰岛素生物标志物的变化是否通过胰岛素调节。使用了一种糖尿病模型，其中涉及了链脲佐菌素（STZ）的施用，该链佐菌素会在大鼠中产生低胰岛素血症。本研究包括接受假手术或胰岛素颗粒治疗的经媒介物或STZ处理的大鼠。两周后，给予大鼠盐水或尼古丁的静脉自我给药（IVSA）的权限。在IVSA的12天内评估了食物摄入，水响应和体重的相应变化。在最后一次会议之后，使用Luminex®技术评估血浆中胰岛素，瘦素，胰岛淀粉样多肽和胰高血糖素样肽1（GLP-1）的水平。在一个单独的队列中，在接受了赋形剂或STZ治疗的大鼠的伏隔核（NAc）和腹侧被盖区（VTA）中评估了磷酸化的胰岛素受体底物2（pIRS-2）和胰岛素生长因子1受体β（IGF-1Rβ）。假手术或胰岛素沉淀。与对照组相比，经STZ处理的大鼠表现出葡萄糖水平的增加，体重的减少以及尼古丁，食物和水的摄入量的增加。与对照组相比，经STZ治疗的大鼠血浆胰岛素和瘦素水平降低，胰岛淀粉样多肽和GLP-1水平升高。重要的是，补充胰岛素可预防所有STZ诱导的行为变化和胰岛素生物标志物。经STZ处理的大鼠在NAc中也显示pIRS-2和IGF-1Rβ降低（但未显示VTA），胰岛素也可以阻止这种作用。
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