No abstract

Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/ kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily. Urine osmolality in tolvaptan-treated rats (1,303 ± 126 mOsM) was restored to control levels by metformin (2,335 ± 273 mOsM) within 3 days and was sustained for up to 10 days. Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation. Outer medullary Na+-K+-2Cl− cotransporter 2 (NKCC2) abundance increased (117%) with AMPK stimulation in control rats but not in V2R-blocked rats. Metformin increased V2R KO mouse urine osmolality within 3 hours, and the increase persisted for up to 12 hours. Metformin increased AQP2 in the V2R KO mice similar to the tolvaptan-treated rats. These results indicate that AMPK activators, such as metformin, might provide a promising treatment for congenital NDI.

Impaired wound healing is commonly encountered in patients with diabetes mellitus, which may lead to severe outcomes such as amputation, if untreated timely. Macrophage plays a critical role in the healing process including the resolution phase. Although magnetic therapy is known to improve microcirculation, its effect on wound healing remains uncertain. In the present study, we found that 0.6 T static magnetic field (SMF) significantly accelerated wound closure and elevated reepithelialization and revascularization in diabetic mice. Notably, SMF promoted the wound healing by skewing the macrophage polarization towards M2 phenotype, thus facilitating the resolution of inflammation. In addition, SMF upregulated anti-inflammatory gene expression via activating STAT6 and suppressing STAT1 in macrophage. Taken together, our results indicate that SMF may be a promising adjuvant therapeutic tool for treating diabetic wounds.

The aim of this study is to investigate the correlation between serum microRNA-217 and the severity of diabetic kidney disease determined by albuminuria. Four hundred ninety five type 2 diabetes patients were divided into three groups: normoalbuminuric group, microalbuminuric group, and macroalbuminuric group. Serum microRNA-217 levels were validated by real-time polymerase chain reaction. Serum silent information regulator 1, Hypoxia-inducible factor-1α and vascular endothelial growth factor were determined by enzyme-linked immunosorbent assay. Compared with control, serum microRNA-217 levels were significantly increased in type 2 diabetes patients and gradually increased in patients of normoalbuminuric, microalbuminuric, and macroalbuminuric groups (P < 0.01). Moreover, increased levels of serum microRNA-217, hypoxia-inducible factor-1α, vascular endothelial growth factor, diabetes mellitus duration, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin resistance, glycated hemoglobin, low-density lipoprotein, total cholesterol, triglyceride, uric acid, serum creatinine, blood urea nitrogen, and decreased levels of serum silent information regulator 1 and high-density lipoprotein were significantly correlated with Ln(ACR) (P < 0.05). In addition, serum microRNA-217 was positively correlated with diabetes mellitus duration, homeostasis model assessment for insulin resistance, glycated hemoglobin, Ln(ACR), low-density lipoprotein, total cholesterol, triglyceride, uric acid, serum creatinine, blood urea nitrogen, hypoxia-inducible factor-1α, vascular endothelial growth factor (P < 0.05), and negatively correlated with serum silent information regulator 1 (P = 0.002). Our findings suggest that microRNA-217 may have an association with the development of proteinuria in type 2 diabetes patients. Serum microRNA-217 may be involved in the development of diabetic kidney disease by promoting chronic inflammation, renal fibrosis, and angiogenesis.