The Impact of Small RNA Interference Against Homer1 on Rats with Type 2 Diabetes and ERK Phosphorylation.
The objective of the study is to evaluate Homer1 expression in rats with Type 2 diabetes mellitus (T2DM) and investigate the mechanism by which Homer1 influences the pathogenesis of diabetes through study on rat model with decreased Homer1 expression. Rat model of T2DM was constructed and blood insulin concentration was measured. Homer1 mRNA and protein expressions in rat pancreatic tissue were determined using RT-PCR as well as Western blotting. Homer1 expression in human monocytic THP-1 cells was interfered using short hairpin RNA, and its effect on phosphorylation of extracellular signal-regulated kinase (ERK) was assessed. Fasting glucose concentration in rat model of T2DM was significantly higher than that of normal rats (13.1 ± 2.4 vs 5.1 ± 1.1 mmol/L), and fasting blood insulin concentration of diabetic group was significantly lower than that of normal group (13.6 ± 1.9 18.3 ± 2.2 mIU/L) (P < 0.05). Homer1 mRNA and protein expressions in pancreatic tissue of rats with T2DM were significantly higher than those of normal rats (P < 0.05). Level of ERK phosphorylation in pancreatic tissue of rats with T2DM was significantly higher than that of normal rats. Homer1 mRNA level in rat pancreatic tissue of T2DM was positively correlated with the area of pancreatic islets (r = 0.526, P = 0.014). Homer1 mRNA level was significantly inhibited in high-glucose and high-fat stimulated human monotypic THP-1 cells with interfered Homer1. Compared with controls, P-ERK phosphorylation was significantly decreased in THP-1 cells with interfered Homer1 (P < 0.05). Homer1 can promote the progression of T2DM, which may be achieved through affecting ERK phosphorylation.
Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710000, Shanxi, China.
Jun
J
Lu
Department of Cardiology, Lanzhou Military General Hospital in Urumqi, Urumqi, 830000, Xinjiang, China.
Jihong
J
Gan
Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710000, Shanxi, China.
Guoqiang
G
Fu
Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710000, Shanxi, China.
Lu
L
Ding
Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710000, Shanxi, China. qsz2088@163.com.
Qiangsun
Q
Zheng
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D000072233:Homer Scaffolding Proteins; D007328:Insulin; D048049:Extracellular Signal-Regulated MAP Kinases
ERK; Homer1; Type 2 diabetes mellitus