التفاصيل البيبلوغرافية
| العنوان: |
Autoimmune activation of the GnRH receptor induces insulin resistance independent of obesity in a female rat model. |
| المؤلفون: |
Li, Hongliang, Zhang, Gege, Guo, Yankai, Deng, Jielin, Fischer, Hayley, Craig, LaTasha B., Kem, David C., Yu, Xichun |
| المصدر: |
Physiological Reports; Jan2021, Vol. 8 Issue 24, p1-10, 10p |
| مصطلحات موضوعية: |
LUTEINIZING hormone releasing hormone receptors, INSULIN receptors, INSULIN resistance, WHITE adipose tissue, GLUCOSE tolerance tests |
| مستخلص: |
Polycystic ovary syndrome (PCOS), a metabolic and reproductive disease, is frequently associated with type 2 diabetes. We have demonstrated activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of the gonadotropin‐releasing hormone receptor (GnRHR) are present in a significant subgroup of PCOS patients. It is unclear whether GnRHR‐AAb can induce peripheral tissue insulin resistance (IR) in animal models. Sixteen rats were divided equally into a GnRHR ECL2 peptide‐immunized group (IMM group) and a control group (CON group). Sera GnRHR‐AAb titer, luteinizing hormone (LH), and testosterone (T) were higher in IMM rats compared with CON rats. No significant difference in fasting blood glucose was observed between the two groups. However, the plasma glucose level at other time points of the IMM group was higher than that of the CON group during an intraperitoneal glucose tolerance test (IPGTT) and an insulin tolerance test (ITT) (p < 0.01). These data support the likelihood of the GnRHR‐AAb induction of glucose intolerance and IR. Compared with the CON group, the IMM group showed a significant increase in insulin‐stimulated phosphorylation of IRS‐1 (p‐IRS‐1 S636/639) and a decrease in insulin‐stimulated phosphorylation of Akt (p‐AKT S473). Expression of the glucose transport genes including GLUT‐2 in liver and GLUT‐4 in white adipose tissue and skeletal muscle was significantly decreased in IMM rats compared with the CON rats. Serum levels of proinflammatory cytokines (TNF‐α, IL‐1α, and IL‐18) were increased, while anti‐inflammatory cytokines (IL‐4 and IL‐10) were decreased in the IMM group. Taken together, elevated GnRHR‐AAb enhanced LH, hyperandrogenism, and inflammation. These changes are likely related to the observed peripheral tissue IR through the downregulation of the insulin‐stimulated IRS/PI3K/Akt/Glut signaling pathway. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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