Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.
Backgrounds: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). Aims: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). Methods: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR). Logistic regression analysis was employed to analyze risk factors associated with DR. Results: NPDR and PDR patients had higher systolic blood pressure (SBP) and higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than the non-DR group (p < 0.05). The prevalence of abnormal ankle-brachial index (ABI) in the non-DR, NPDR, and PDR groups was 7.00, 10.80, and 13.96%, respectively (p < 0.05) and the prevalence of peripheral arterial plaques was 68.48, 81.38, and 80.56%, respectively (p < 0.001). Logistic regression analysis showed that DR (vs. non-DR) was associated with peripheral arterial plaques (OR = 2.07), SBP ≥130 mm Hg (OR = 1.53) and levels of hemoglobin (Hb)A1c (OR = 2.11) and TC (OR = 1.42). Conclusion: PAD is commonly associated with NPDR and PDR. Hypercholesterolemia is an important risk factor for the development of PAD and CVD in patients with DR. Our results suggest that a routine ABI test, duplex ultrasonography, and obtaining a lipid profile for DR patients may help to reduce the occurrence of PAD and CVD.
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