Bone morphogenetic protein 7 regulates insulin signal transduction in mice

Objective To analyze the effects of bone morphogenetic protein 7 (BMP 7) on insulin signaling pathway in mice and its involved molecular mechanisms. Methods To increase BMP7 expression in liver, adenovirus bearing BMP7 was injected into mice via tail vein. The impact of BMP7 overexpression on glucose metabolism was assayed by glucose tolerance test and insulin tolerance test. The levels of proteins involved in insulin signaling pathway and c-Jun N-terminal kinase (JNK) signaling pathway were analyzed by Western blot. Results The blood glucose level was increased by BMP7 overexpression (P<0.05), while the glucose tolerance and insulin tolerance were decreased by BMP7. The p-Akt and p-GSK3β in liver and epididymal white adipose tissue (WAT) were reduced in the BMP7-overexpressed mice (P<0.01), indicating insulin signal transduction was inhibited. In gastrocnemius muscle, the insulin signal transduction was not altered by BMP7. Mechanistically, the JNK pathway was activated by BMP7 in liver and epididymal WAT (P<0.01), while the JNK pathway in skeletal muscle was not changed. Conclusions In mice, BMP7 elevated blood sugar and decreased glucose and insulin tolerance. BMP7 inhibited the insulin signaling pathway in liver and WAT. These inhibitory effects on insulin signaling pathway was likely to be achieved by an activating JNK signaling pathway. (Chin J Endocrinol Metab, 2018, 34: 398-403) Key words: Bone morphogenetic protein 7; Insulin signaling transduction; JNK; Insulin resistance; Diabetes mellitus, experimental