miR-335-5p induces insulin resistance and pancreatic islet ß-cell secretion in gestational diabetes mellitus mice through VASH1-mediated TGF-ß signaling pathway.

Multiple studies have reported different methods in treating gestational diabetes mellitus (GDM); however, the relationship between miR-335-5p and GDM still remains unclear. Here, this study explores the effect of miR-335-5p on insulin resistance and pancreatic islet ß-cell secretion via activation of the TGFß signaling pathway by downregulating VASH1 expression in GDM mice. The GDM mouse model was established and mainly treated with miR-335-5p mimic, miR-335-5p inhibitor, si-VASH1, and miR-335-5p inhibitor + si-VASH1. Oral glucose tolerance test (OGTT) was conducted to detect fasting blood glucose (FBG) fasting insulin (FINS). The OGTT was also used to calculate a homeostasis model assessment of insulin resistance (HOMA-IR). A hyperglycemic clamp was performed to measure the glucose infusion rate (GIR), which estimated ß-cell function. Expressions of miR-335-5p, VASH1, TGF-ß1, and c-Myc in pancreatic islet ß-cells were determined by RT-qPCR, western blot analysis, and insulin release by ELISA. The miR-335-5p mimic and si-VASH1 groups showed elevated blood glucose levels, glucose area under the curve (GAUC), and HOMA-IR, but a reduced GIR and positive expression of VASH1. Overexpression of miR-335-5p and inhibition of VASH1 contributed to activated TGFß1 pathway, higher c-Myc, and lower VASH1 expressions, in addition to downregulated insulin and insulin release levels. These findings provided evidence that miR-335-5p enhanced insulin resistance and suppressed pancreatic islet ß-cell secretion by inhibiting VASH1, eventually activating the TGF-ß pathway in GDM mice, which provides more clinical insight on the GDM treatment.

[Relationship between different renal functional state with therapeutic effect on diabetic foot ulcers].

OBJECTIVE: To study the relationship between renal functional state and the therapeutic effect and prognosis of foot ulcers in the patients with diabetic mellitus. METHODS: The renal function was evaluated in term of glomerular filtration rate, microalbuminuria, proteinuria, blood urea nitrogen (BUN) and creatinine (Cr) levels in 126 patients with I-V class diabetic foot ulcers (according to Wagner classic standard) before the treatment, and then these patients were divided into 1-5 classes (according to Mogenson standard) and given systemic treatment and local debridement, with astragalus for topical application. The time of growth of granulation tissue (GT), the time of healing (HT), the amputation rate and mortality were observed. RESULTS: GT and HT of ulcer prolonged with worsening of diabetic nephropathy regardless of the disease phase of foot ulcers, especially the GT and HT of foot ulcers were significantly longer in IV and V phases of diabetic nephropathy than those of III phase diabetic nephropathy though the conditions of their foot ulcers were about the same. GT and HT in all the patients with the foot ulcers in the similar condition exhibited significantly positive linear correlation with the severity of diabetic nephropathy (r(1)=2.344 and r(2)=2.563, respectively, both P<0.05). The mortality of I-III phase diabetic nephropathy was significantly lower than that of IV and V phase diabetic nephropathy when the foot ulcers of these patients were of the same extent (P<0.05). CONCLUSION: A worsening of renal function would affect the treatment effect and prognosis of foot ulcers in the patients with diabetic foot ulcers, implicating that it is very important to improve the renal function in the treatment of patients with diabetic foot ulcers.