Therapeutic Strategies and Screening Methods for PKC epsilon antagonists in the treatment of Type 2 diabetes

PKC ε拮抗剂治疗2型糖尿病的治疗策略和筛选方法

• 批准号: nhmrc : 427629
• 负责人: A/Pr Carsten Schmitz-Peiffer
• 金额: $ 10.49万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Development Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/therapeutic-strategies-screening-2-diabetes/99348
• 关键词: Therapeutic; Strategies; Screening; Methods; PKC

Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.

2型糖尿病是一种慢性疾病，影响着超过100万澳大利亚人和全世界数亿人。它的患病率正在上升，由于几个因素，如增加热量摄入，人口老龄化，以及西方文明的常见久坐不动的生活方式。2型糖尿病发生在胰腺无法产生足够的胰岛素供身体科普餐后血糖水平升高时，并且与肥胖密切相关。我们现在已经证明，胰腺中发现的一种酶在脂肪供应过剩的条件下被不适当地激活，并且在胰腺响应葡萄糖而释放胰岛素的缺陷的发展中起重要作用。令人兴奋的是，我们还表明，一旦这些缺陷建立，抑制这种酶可以部分逆转这些缺陷。我们现在打算进一步验证这种酶作为药物靶点，通过确定在小鼠模型中治疗2型糖尿病的最佳给药方案，并测试这种方法是否可以与先前开发的促进胰岛素作用的药物结合使用，以改善血糖处理，优于单独治疗。这将促进酶作为治疗2型糖尿病的治疗策略。我们还计划开发一种高通量筛选方法，以识别该酶的新型抑制剂，这将进一步增加该项目对制药公司的吸引力，这些公司能够更好地将我们的发现完全商业化。