Using pre-clinical biomarkers and epidemiological models to assess the effects of cannabinoids on disease

使用临床前生物标志物和流行病学模型评估大麻素对疾病的影响

基本信息

批准号：
9033247
负责人：
Omayma O Alshaarawy
金额：
$ 9.06万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9033247
关键词：
Adipocytes Adult Animal Model Anti-Inflammatory Agents Anti-inflammatory Antioxidants Attention Award Baltimore Beta Cell Biological Biological Assay Biological Markers Blood Pressure Body mass index CNR1 gene CNR2 gene Cannabinoids Cannabis Catchment Area Cell physiology Cholesterol Chronic Cities Clinical Cohort Studies Collaborations Communities Community Health Competence Coronary Artery Risk Development in Young Adults Study Data Development Development Plans Diabetes Mellitus Diet Disease Environment Epidemiologic Studies Epidemiologist Epidemiology Fatty Acids Funding Future Goals Health Health Surveys Hepatocyte Hyperphagia Immune response Immune system Inflammation Inflammatory Insulin Insulin Resistance Interdisciplinary Study Intervention Islet Cell Islets of Langerhans Knock-out Laboratories Lead Link Longitudinal Studies Marijuana Smoking Measurement Metabolic Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome Oxidative Stress Pancreas Pathway interactions Physicians Policies Population Procedures Productivity Prospective Studies Public Health Publishing Receptor Activation Recruitment Activity Reporting Research Research Design Risk Risk Factors Role Sampling Science Scientist Site Study Section Testing Thinking Time Training Translational Research Woman Work aged bench to bedside biological adaptation to stress biracial cardiometabolic risk career career development clinical biomarkers cohort design diabetes control epidemiological model glucose metabolism human data improved inflammatory marker insulin secretion longitudinal design men mouse model population based pre-clinical preclinical study prevent programs prospective protective effect public health relevance research and development research study skills waist circumference

项目摘要

DESCRIPTION (provided by applicant): There are several scientific puzzles to be solved at the intersection of diabetes mellitus epidemiology, obesity epidemiology, and cannabis smoking epidemiology. On one hand, the 'munchies' reported after cannabis smoking might lead one to think there would be cannabis-attributable obesity and also possibly cannabis attributable type 2 diabetes. Moreover, there is preclinical evidence from animal models that cannabinoid exposure might accelerate type 2 diabetes via the activation of cannabinoid-1 (CB1) receptors, both centrally and hence stimulating hyperphagia, or peripherally in the white adipose cells or the liver cells and in that case promoting de novo fatty acid synthesis and subsequent insulin resistance. On the other hand, rigorously gathered epidemiological evidence from cross-sectional large population based studies supports the idea that cannabis smoking is associated with a reduced occurrence of obesity, a reduced occurrence of diabetes, and lower levels of biomarkers indicative of altered glucose metabolism. Solutions to the cannabis smoking- diabetes puzzle might be found by looking at oxidative stress and immune response pathways that lead toward type 2 diabetes, but for which there is preclinical evidence and some recently published human data that some cannabinoids are immunomodulatory and possibly anti-oxidant in the direction of protection from diabetes. This application is for five years of K99/R00 award support of clinical translational research career development that will make it possible for me to focus my attention on the intriguing possibility that cannabis smoking might be protective against type 2 diabetes, and to produce more definitive evidence from my own bench-to-bedside-to- community studies of cannabinoids and health outcomes, even if the cannabis-diabetes association turns out to be spurious. As a physician epidemiologist, I already am well-prepared for many facets of epidemiological analyses, as noted in my preliminary studies section. Sustained translational cannabinoid-health research is what motivates the two inter-connected parts of my research development plan: (1) my mastery of preclinical and laboratory science skill sets that will prepare me to design new bench science experiments to gain more definitive evidence on the suspected mechanisms linking cannabis exposure and health, and (2) my mastery of the design and conduct of large sample epidemiological prospective studies and field experiments, as required to enhance our understanding of cannabis health effects.

描述（由申请人提供）：糖尿病流行病学、肥胖流行病学和吸食大麻流行病学的交叉点有几个科学难题需要解决。一方面，吸食大麻后报告的“零食”可能会让人们认为会有这样的情况。此外，动物模型的临床前证据表明，接触大麻素可能会通过激活 2 型糖尿病而加速 2 型糖尿病的发生。大麻素-1（CB1）受体，既可以在中枢刺激食欲亢进，也可以在白色脂肪细胞或肝细胞的外周，促进从头脂肪酸合成和随后的胰岛素抵抗。另一方面，严格收集的流行病学证据。来自大规模人口的横断面研究支持这样的观点，即吸食大麻与减少肥胖发生率、减少糖尿病发生率以及指示葡萄糖代谢改变的生物标志物水平较低有关，解决吸食大麻与糖尿病之谜可能是这样的。成立通过研究导致 2 型糖尿病的氧化应激和免疫反应途径，但临床前证据和最近发表的一些人体数据表明，某些大麻素具有免疫调节作用，并且可能具有抗氧化作用，可在五年内预防糖尿病。 K99/R00 奖项支持临床转化研究职业发展，这将使我能够将注意力集中在吸食大麻可能预防 2 型糖尿病这一有趣的可能性上，并从我的研究中提供更明确的证据。我自己对大麻素和健康结果进行了从实验室到临床到社区的研究，即使大麻与糖尿病的关联被证明是虚假的，作为一名医生流行病学家，我已经为流行病学分析的许多方面做好了充分的准备。在我的初步研究部分，持续的转化大麻素健康研究推动了我的研究发展计划的两个相互关联的部分：（1）我对临床前和实验室科学技能的掌握，这将为我做好准备。设计新的台架科学实验，以获得关于大麻暴露与健康之间的可疑机制的更明确的证据，以及（2）我掌握大样本流行病学前瞻性研究和现场实验的设计和进行，以增强我们对大麻的了解健康影响。