在糖尿病中,胰岛素分泌受损和胰岛素抵抗导致高甘油三酯血症,脂蛋白脂肪酶(LPL)的酶活性取决于胰岛素的作用。LPL向内皮细胞的转运及其酶活性通过脂肪分解复合物的形成来维持,这取决于多重阳性(糖基磷脂酰肌醇锚定的高密度脂蛋白结合蛋白1[GPIHBP1],载脂蛋白C-II[APOC2],APOA5,硫酸乙酰肝素蛋白聚糖[HSPG],脂肪酶成熟因子1[LFM1]和lin-12样的sel-1抑制因子[SEL1L])和负调节因子(APOC1,APOC3,血管生成素样蛋白[ANGPTL]3,ANGPTL4和ANGPTL8)。在监管机构中,GPIHBP1是LPL从实质细胞易位到毛细血管内皮细胞腔表面的关键分子,和维持脂解活性;也就是说,甘油三酯水解成游离脂肪酸和单甘油酯,并在外源途径中从乳糜微粒转化为乳糜微粒残留物,在内源途径中从极低密度脂蛋白转化为低密度脂蛋白。GPIHBP1的无效突变导致严重的高甘油三酯血症和胰腺炎,GPIGBP1自身抗体综合征也会导致严重的高甘油三酯血症和急性胰腺炎的反复发作.在2型糖尿病患者中,血清甘油三酯水平升高与循环LPL水平负相关,与循环APOC1、APOC3、ANGPTL3、ANGPTL4和ANGPTL8水平呈正相关。相比之下,循环GPIHBP1水平在2型糖尿病患者血清甘油三酯水平较高,而在有糖尿病视网膜病变和肾病的2型糖尿病患者中,它们升高。脂解复合物的循环调节剂可能是脂质和葡萄糖代谢的新生物标志物,和糖尿病血管并发症。
In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [
GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators,
GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of
GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating
GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.