NICOTINE & MORPHINE EFFECTS ON DIABETES ONSET & COMPLICATIONS

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，在美国每年消耗约15%的医疗费用。与此同时，36%的人口吸烟，阿片类药物也是最常滥用的药物之一。本研究的长期目标是检验假设1）急性或慢性给予尼古丁或吗啡加速糖尿病的发作。2)糖尿病并发症在长期摄入尼古丁/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性（即，阿片受体、烟碱受体和毒蕈碱受体）。A）为了评价吗啡和尼古丁对糖尿病发作的影响，将用尼古丁和吗啡急性或慢性处理大鼠，然后用不同剂量的链脲佐菌素（20、40、60 mg/kg）腹膜内攻击以诱导糖尿病。B）为了检查吗啡和尼古丁对糖尿病状态的影响，首先通过腹膜内注射60 mg/kg链脲佐菌素（STZ）使大鼠患糖尿病。然后对这些糖尿病大鼠进行尼古丁长期给药（8周）。这些大鼠中的一些组也将用胰岛素治疗。控制将接收车辆。在八周期间，待监测的参数包括：可能发生的腹泻/便秘、体重、液体消耗、来自尾部切口的血糖水平。在给药期结束时，将通过断头处死动物，并通过特定诊断试剂盒测量血液胰岛素和葡萄糖水平等参数，还将检查胰腺的组织病理学。C）将进行放射性配体结合研究以确定经处理和未经处理的大鼠中阿片受体、烟碱受体和毒蕈碱受体的受体密度。检查注意力的影响，因为相当数量的美国人口和世界人口患有成瘾，同时也可能患有糖尿病。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，并可能为制定新的治疗策略提供重要的实用信息。

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.