Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
MEDOC Department, Max Super Speciality Hospital, Bathinda, 151001, Punjab, India.
Mol Neurobiol. 2024 Nov;61(11):8656-8667. doi: 10.1007/s12035-024-04127-2. Epub 2024 Mar 27.
Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications.
2 型糖尿病（T2DM）患者的长期高血糖状态会导致肾脏、视网膜、皮肤和神经元组织等多种器官和组织发生病理性和功能性损伤，进而引发微血管糖尿病并发症。已有研究报道，肾素-血管紧张素-醛固酮系统（RAAS）途径的改变在 T2DM 及相关并发症患者胰岛素抵抗的发生发展中起着重要作用。本研究旨在评估无并发症的 T2DM 患者和有并发症（视网膜病变、肾病和神经病变）的 T2DM 患者的 RAAS 基因表达改变与危险因素的相关性。本研究共纳入 420 名受试者，包括 140 名健康对照者、140 名有并发症的 T2DM 患者和 140 名无并发症的 T2DM 患者。评估了与 T2DM 及糖尿病并发症发生发展相关的危险因素。此外，还采用 qRT-PCR 法检测了健康对照组、有并发症的 T2DM 患者和无并发症的 T2DM 患者中 RAAS 基因（AGT、ACE、ACE2 和 AGT1R）的表达情况。研究发现，城市背景、较高的 BMI、酗酒、吸烟和糖尿病家族史等多种危险因素与 T2DM 及糖尿病并发症的发生有关。与对照组相比，有并发症的 T2DM 患者和无并发症的 T2DM 患者中 AGT、ACE 和 AGT1R 的表达水平升高，而 ACE2 的表达水平降低。RAAS 途径研究基因的表达改变与微血管糖尿病并发症的发生有关。
