通过PGK1/AKT激活,伊索哈姆尼丁作为糖尿病的潜在治疗剂
Abdelrahim Alqudah1, Esam Qnais2, Mohammed Alqudah3
1Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.
Archives of physiology and biochemistry
|March 6, 2024
概括
伊索哈姆尼丁通过改善胰岛素敏感性和降低葡萄糖水平,显示出对2型糖尿病 (T2D) 管理的前景. 这种天然化合物有效地对抗氧化和糖性压力,提供了一种新的治疗策略.
科学领域:
- 生物化学和分子生物学
- 药理学 药理学是指药理学的学科.
- 内分泌学 在内分泌学.
背景情况:
- 2型糖尿病 (T2D) 是一个全球性的健康挑战,需要新的治疗策略.
- 对于T2D的传统治疗有局限性,这推动了对新型干预措施的搜索.
研究的目的:
- 为了研究异黄hamnetin在提高胰岛素敏感性的潜力.
- 通过调节氧化和糖性压力来评估异姆尼丁在减轻T2D特征方面的有效性.
主要方法:
- 在小鼠中使用高脂肪饮食和 estreptozotocin 诱导T2D; isorhamnetin 被口服12周.
- 在体外研究中使用了HepG2细胞来评估异胺对压力标志物和胰岛素敏感性的影响.
- 分子分析的重点是糖酸激酶1 (PGK1) 和AKT信号通路.
主要成果:
- 伊索拉姆尼丁在HepG2细胞和体内显著降低了氧化和糖性压力标志物.
- 接受治疗的小鼠表现出更低的禁食葡萄糖水平,改善的葡萄糖耐受性和增强的胰岛素敏感性.
- 伊索哈姆尼丁激活了PGK1/AKT通路,这对于葡萄糖吸收和减少胰岛素抵抗至关重要.
结论:
- 伊索拉姆尼丁作为T2D管理的治疗剂具有显著的潜力.
- 该化合物的减轻压力和调节关键分子通路的能力为改善胰岛素敏感性提供了一种新的方法.
- 需要进一步的临床研究来将这些临床前发现转化为有效的T2D治疗方法.
相关概念视频
Glucagon-like Receptor Agonists
321
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...
321
Oral Hypoglycemic Agents: Glinides
154
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...
154
Dipeptidyl Peptidase 4 Inhibitors
186
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...
186
Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
Hormones Regulating Blood Glucose
3.3K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
3.3K
Oral Hypoglycemic Agents: Biguanides and Glitazones
199
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...
199


