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.

这项研究是为了研究滥用药物，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，在美国消耗了约15％的年度医疗支出。同时，有36％的人口吸烟，而阿片类药物在普遍的虐待药物中也排名很高。这项研究的长期目标是检查假设1）急性或长期施用的尼古丁或吗啡会加速糖尿病的发作。 2）糖尿病并发症在慢性摄入的尼古丁/吗啡的影响下恶化。 3）糖尿病的退化过程将改变吗啡和尼古丁受体的受体结合特征（即阿片受体，烟碱受体和毒蕈碱受体）。我们将考虑到以下特定目的检查这些假设：a）评估吗啡和尼古丁对糖尿病发作的作用，将用尼古丁和吗啡治疗大鼠，急性或慢性地及其随后以各种剂量的链链球菌素（20，40，60 mg/kg）的糖尿病来构成糖尿病。 b）检查吗啡和尼古丁对糖尿病状态的影响，首先将大鼠腹腔内注射60 mg/kg的链霉菌素（STZ）。然后，这些糖尿病大鼠将接受尼古丁的长期给药（8周）。这些大鼠的一些组也将用胰岛素治疗。控件将接收车辆。在八周内，要监视的参数包括：可能出现腹泻/便秘，体重，液体消耗，血糖水平，从尾部的切口出现。在治疗期结束时，将通过斩首和诸如血液胰岛素和葡萄糖水平等参数杀死动物，通过特定的诊断试剂盒进行测量，还将检查胰腺的组织病理学。 c）将进行无线电配体结合研究，以确定治疗和未处理大鼠中阿片受体，烟碱受体和毒蕈碱受体的受体密度。检查注意力的影响是因为美国大量人口和世界人口遭受成瘾的困扰，并且可能同时患有糖尿病。拟议的研究可能会增加对糖尿病药物滥用的基本机制的理解，并可能为制定新的治疗策略提供重要的实用信息。