Department of Laboratory Medicine, AIIMS, New Delhi, India.
Department of Laboratory Medicine, All India Institute of Medical Sciences, Room No. 11, 2nd Floor, New Delhi, India.
Mol Cell Biochem. 2024 May;479(5):1109-1120. doi: 10.1007/s11010-023-04782-4. Epub 2023 Jun 20.
Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1β, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.
在应激条件下，肝脏、心脏和胰腺中会产生大量的各种毒性自由基，这些自由基经常会被多个平行因子检测到。它们积极参与糖尿病和代谢异常的发展。然而，在患有糖尿病和代谢异常的患者以及未被诊断出患有糖尿病和代谢异常的个体中，GDF-15mRNA 的过度激活和铁转运基因的铁流入是否直接抑制了 Nrf-2 基因？因此，我们研究了糖尿病和代谢综合征中 Zip8/14mRNA、GDF-15mRNA 和 Nrf-2mRNA 的表达，预计到 2045 年，印度的糖尿病和代谢综合征患者将达到 1.34 亿。我们从印度新德里全印度医学科学研究所医学系内分泌代谢诊所招募了 120 名受试者。在糖尿病、代谢综合征、糖尿病伴代谢异常和健康对照组中测量了与人体测量学、营养、血液学、生物化学、细胞因子和氧化应激相关的各种研究。在所有受试者中进行了 GDF-15、ZIP8、ZIP14、Nrf-2 和管家基因的相对表达。应激反应细胞因子在代谢异常患者中表达较高，与体重、IR、腰围和脂肪量有关。代谢综合征中 IL-1β、TNF-α 和 IL-6 水平显著升高，而脂联素水平显著降低。糖尿病伴代谢综合征时 MDA 水平升高，而 SOD 活性降低（p=0.001）。与第 I 组相比，第 III 组 GDF-15mRNA 表达上调 1.79 倍，而糖尿病伴代谢异常组 Nrf-2 表达下调 2-3 倍。Zip8mRNA 表达下调（p=0.014），Zip14mRNA 表达上调（p=0.06）在糖尿病和代谢异常中。发现 GDF-15 和 Nrf-2mRNA 表达之间存在关联，并且与 ROS 高度相关。Zip8/14mRNA 的表达也在糖尿病和代谢相关并发症中失调。
