<br>关于葡萄糖激酶和葡萄糖激酶调节蛋白在糖尿病中的作用的最新见解,Mini-Reviews in Medicinal Chemistry

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关于葡萄糖激酶和葡萄糖激酶调节蛋白在糖尿病中的作用的最新见解
Mini-Reviews in Medicinal Chemistry ( IF 3.3 ) Pub Date : 2023-09-12 , DOI: 10.2174/1389557523666230823151927
Ajita Paliwal ₁ , Vartika Paliwal ₁ , Smita Jain ₁ , Sarvesh Paliwal ₁ , Swapnil Sharma ₁

Affiliation

葡萄糖激酶调节剂 (GCKR) 基因编码葡萄糖激酶 (GCK) 抑制剂，仅存在于肝细胞中，负责葡萄糖代谢。在全基因组关联研究中，常见的 GCKR 编码变异与各种代谢特征相关。罕见的 GCKR 多态性影响 GKRP 活性、表达和定位。尽管不是原因，但这些变异与高甘油三酯血症有关。由于它们的晶体结构，我们现在更好地了解 GKRP 和 GCK 之间的分子相互作用。最后，已经鉴定出与 GKRP 特异性结合并降低糖尿病模型血糖水平的小分子。 GCKR 等位基因谱变化影响脂质和葡萄糖稳态。根据功能分析，GKRP 功能障碍与多种分子原因有关。大量研究表明，GKRP 功能障碍并不是高甘油三酯血症的唯一原因，这意味着可以通过小分子 GKRP 抑制激活肝脏特异性 GCK 来治疗 2 型糖尿病。该综述强调了目前关于葡萄糖激酶和 GKRP 在肝糖代谢和糖尿病中的特征性作用的发现。这些信息影响了糖尿病定向分子疗法的发展，从而提高了我们对脂质和葡萄糖生理学的理解。

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Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes

The glucokinase regulator (GCKR) gene encodes an inhibitor of the glucokinase enzyme (GCK), found only in hepatocytes and responsible for glucose metabolism. A common GCKR coding variation has been linked to various metabolic traits in genome-wide association studies. Rare GCKR polymorphisms influence GKRP activity, expression, and localization. Despite not being the cause, these variations are linked to hypertriglyceridemia. Because of their crystal structures, we now better understand the molecular interactions between GKRP and the GCK. Finally, small molecules that specifically bind to GKRP and decrease blood sugar levels in diabetic models have been identified. GCKR allelic spectrum changes affect lipid and glucose homeostasis. GKRP dysfunction has been linked to a variety of molecular causes, according to functional analysis. Numerous studies have shown that GKRP dysfunction is not the only cause of hypertriglyceridemia, implying that type 2 diabetes could be treated by activating liver-specific GCK via small molecule GKRP inhibition. The review emphasizes current discoveries concerning the characteristic roles of glucokinase and GKRP in hepatic glucose metabolism and diabetes. This information has influenced the growth of directed molecular therapies for diabetes, which has improved our understanding of lipid and glucose physiology.

更新日期：2023-09-12

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