Abnormal glucose metabolism in heterozygous mutant mice for a type I receptor required for BMP signaling.
BMPRIA 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 Ins2 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 BMPRIA plays an important role in glucose metabolism and possibly working through the GSIS pathway.
Knock Out Core, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Gregory J
GJ
Scott
Manas K
MK
Ray
Toni
T
Ward
Kelly
K
McCann
Shyamal
S
Peddada
Fang-Xu
FX
Jiang
Yuji
Y
Mishina
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test / Q000706:statistics & numerical data; D006579:Heterozygote; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011384:Proinsulin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D001786:Blood Glucose; D019485:Bone Morphogenetic Proteins; C514817:Ins1 protein, mouse; D007328:Insulin; D012333:RNA, Messenger; D011384:Proinsulin; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D005947:Glucose