RESUMEN
Nail-patella syndrome (NPS) is a hereditary disease caused by pathogenic variants in LMX1B and characterized by nail, limb, and renal symptoms. This study revealed a likely pathogenic LMX1B variant, NM_002316.4: c.723_726delinsC (p.Ser242del), in Japanese twins with clubfoot. The patients' mother, who shared this variant, developed proteinuria after delivery. p.Ser242del is located in the homeodomain of the protein, in which variants that cause renal disease tend to cluster. Our findings highlight p.Ser242del as a likely pathogenic variant, expanding our knowledge of NPS.
RESUMEN
Enhancement of AT1 receptor-associated protein (ATRAP) in adipose tissue improves high fat diet (HFD)-induced visceral obesity and insulin resistance, and suppresses adipose oxidative stress. However, HFD loading is not a direct stimulatory factor for AT1 receptor. In the present study, we investigated the effect of chronic, low-dose angiotensin II (Ang II) stimulation on glucose and lipid metabolism in mice and functional role of ATRAP. ATRAP expression was higher in adipose tissue (5-10-fold) and skeletal muscle tissue (approximately 1.6-fold) in ATRAP transgenic (TG) mice compared with wild-type (WT) mice. After Ang II infusion, insulin sensitivity was impaired in WT mice, but this response was suppressed in TG mice. Unexpectedly, Ang II infusion did not affect the adipose tissue profile in WT or TG mice. However, in skeletal muscle tissue, Ang II stimulus caused an increase in oxidative stress and activation of p38 MAPK, resulting in a decrease in glucose transporter type 4 expression in WT mice. These responses were suppressed in TG mice. Our study suggests that Ang II-induced insulin resistance is suppressed by increased ATRAP expression in skeletal muscle tissue. Hyperactivity of AT1 receptor could be related to formation of insulin resistance related to metabolic syndrome.