Abnormal Glucose Metabolism in Heterozygous Mutant Mice for a Type I Receptor Required for BMP Signaling

作者：Scott Gregory J; Ray Manas K^*; Ward Toni; McCann Kelly; Peddada Shyamal; Jiang Fang Xu; Mishina Yuji

来源：Genesis, 2009, 47(6): 385-391.

DOI：10.1002/dvg.20513

• bone morphogenetic protein (BMP)
• bone morphogenetic protein receptor (BMPR)
• insulin
• intraperitoneal glucose tolerance test (IPGTT)
• diabetes
• heterozygous mutant mice
• heterozygous phenotype
• pancreas

BMPR1A and its high-affinity ligand BMP4 have recently been shown to be expressed in the beta-cells of the pancreas. Here, we report the abnormalities of heterozygous mice for Bmpr1a in glucose metabolism during the course of intraperitoneal glucose tolerance test. The heterozygous mice had increased blood glucose levels throughout the first 2.5 h after the administration of glucose. Analysis of glucose-stimulated insulin secretion (GSIS) indicates that insulin secretion in the heterozygous mice is compromised, and induction of secreted insulin by stimulation is substantially lower compared with the wild-type controls. No apparent abnormalities in pancreas, thyroid, and liver were seen upon histological examination. Real-time PCR results of selected genes showed an increase in the mRNA level of Ins1 and 1ns2 in the heterozygous group. These results indicate that the glucose-sensing pathway in these heterozygous mice is altered because of the heterozygosity in Bmpr1a. Together, our data suggest that BMP signaling through BMPR1A plays an important role in glucose metabolism and possibly working through the GSIS pathway. genesis 47:385-391, 2009.

• 出版日期2009-6
• 单位河北医科大学