NICOTINE & MORPHINE EFFECTS ON DIABETES ONSET & COMPLICATIONS

尼古丁

• 批准号: 6318332
• 负责人: Patience O Obih
• 金额: $ 5.71万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6318332
• 关键词: blood glucose; disease /disorder model; disease /disorder onset; drug related diabetes mellitus; histopathology; insulin; laboratory rat; morphine; nicotine; opioid receptor; receptor binding

This study is undertaken to investigate the effect of drugs of abuse, morphine and nicotine on diabetes mellitus. Diabetes mellitus is the most common endocrine disease and consumes about 15% of annual health care expenditure in the United States. At the same time 36% of the population smokes cigarette and the opiates also rank high among the commonly abused agents. The long term goal of this study is to examine the hypothesis 1) Acutely or chronically administered nicotine or morphine accelerates the onset of diabetes. 2) Complications of diabetes worsen under the influence of chronically ingested nicotine/morphine. 3) the degenerative processes of diabetes will alter the receptor binding characteristics of morphine and nicotine receptor (ie. opioid receptors, nicotinic receptors and muscarinic receptors). We will examine these hypotheses with the following specific aims in mind: A) To evaluate the effect of morphine and nicotine on the onset of diabetes, rats will be treated with nicotine and morphine acutely or chronically and thereafter challenged with varying doses of streptozotocin (20, 40, 60 mg/kg)) intraperitoneally to induce diabetes. B) To examine the impact of morphine and nicotine on diabetic state, rats will first of all be made diabetic with intraperitonial injection of 60 mg/kg of streptozotocin (STZ). These diabetic rats will then be subjected to chronic administration of nicotine (8 weeks). Some groups of these rats will also be treated with insulin. The control will receive the vehicle. During the eight weeks, parameters to be monitored include: possible occurrence of diarrhea/constipation, body weight, fluid consumption, blood glucose level from an incision on the tail. At the end of the treatment period, animals will be killed by decapitation and parameters such as blood insulin and glucose level, by specific diagnostic kits will be measured, histopathology of the pancreas will also be examined. C) Radio ligand binding studies will be carried out to determine the receptor density of opioid receptors, nicotinic receptors, and muscarinic receptors in the treated and untreated rats. Examining the impact of attention since a significant number of US population and the world population suffer from addiction and may also have diabetes at the same time. The proposed study may increase the understanding of basic mechanisms of drug abuse in diabetes and may provide important practical information for developing new strategies for treatment.

本研究旨在探讨滥用药物、吗啡和尼古丁对糖尿病的影响。糖尿病是最常见的内分泌疾病，占美国每年医疗保健支出的15%左右。与此同时，36%的人口吸烟，鸦片类药物在常见滥用药物中也名列前茅。这项研究的长期目标是检验以下假设：1)急性或长期服用尼古丁或吗啡会加速糖尿病的发病。2)长期摄入尼古丁/吗啡可加重糖尿病并发症。3)糖尿病的退变过程会改变吗啡和尼古丁受体的结合特性。阿片受体、尼古丁受体和毒扁豆碱受体)。A)为了评估吗啡和尼古丁对糖尿病发病的影响，我们将急性或慢性地给予大鼠尼古丁和吗啡治疗，然后用不同剂量的链脲佐菌素(20、40、60 mg/kg)激发大鼠，以诱导糖尿病。2)为了研究吗啡和尼古丁对糖尿病状态的影响，首先用链脲佐菌素(STZ)60 mg/kg腹腔注射复制糖尿病大鼠模型。然后，这些糖尿病大鼠将受到长期尼古丁的影响(8周)。这些大鼠中的一些组也将接受胰岛素治疗。控制人员将接收车辆。在8周内，需要监测的参数包括：可能发生的腹泻/便秘、体重、液体消耗量、从尾部切开的血糖水平。在治疗期结束时，动物将被断头处死，血液胰岛素和血糖水平等参数将通过特定的诊断试剂盒进行测量，胰腺的组织病理学也将被检查。C)将进行放射性配基结合研究，以确定阿片受体、尼古丁受体和毒扁豆碱受体在治疗和未治疗大鼠中的受体密度。考察注意力的影响，因为相当数量的美国人口和世界人口患有毒瘾，并可能同时患有糖尿病。这项拟议的研究可能会增加对糖尿病药物滥用基本机制的理解，并可能为开发新的治疗策略提供重要的实用信息。