一个基因支持的药物重用管道用于糖尿病治疗,使用电子健康记录
Megan M Shuey1, Kyung Min Lee2, Jacob Keaton3
1Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
EBioMedicine
|July 3, 2023
概括
通道阻断剂 (CCB) 显示出降低2型糖尿病患者的血糖水平的希望. 这种药物重定向策略提供了一种低成本的方法,用于发现并发性疾病的新疗法.
科学领域:
- 药理学 药理学是指药理学的学科.
- 遗传学 是一个遗传学.
- 流行病学 流行病学
背景情况:
- 药物重定向提供了一种具有成本效益的方法来确定新的治疗方法.
- 现有的药物可能对伴随性疾病,如血糖控制,有好处.
研究的目的:
- 开发和测试一种基因信息的药物重用管道,用于管理2型糖尿病.
- 确定可以改善血糖控制的现有药物.
主要方法:
- 绘制基因预测的基因表达信号,从全基因组关联研究到药物点.
- 使用自控病例系列 (SCCS) 和门德尔随机化 (MR) 验证的药物基因对.
主要成果:
- 20个候选药物-基因对得到了验证.
- 通道阻断剂 (CCBs) 显示出显著的证据表明血糖降低.
- CCBs显示HbA1c (-0.11%) 和葡萄糖水平 (-0.85 mg/dL) 的降低.
结论:
- 通道阻断剂 (CCB) 是降低血糖水平的强有力的候选者.
- 开发的药物再利用管道可以适应其他治疗领域.
- 这种方法支持发现现有药物的新用途.
相关概念视频
Glucagon-like Receptor Agonists
365
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
365
Oral Hypoglycemic Agents: Glinides
189
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
189
Oral Hypoglycemic Agents: Biguanides and Glitazones
238
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
238
Diabetes: Management and Pharmacotherapy
319
The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
319
Insulin: Dosing Regimen and Adverse Effects
213
Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
213
Dipeptidyl Peptidase 4 Inhibitors
214
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
214


