| First Author | Malakauskas SM | Year | 2009 |
| Journal | Mol Endocrinol | Volume | 23 |
| Issue | 6 | Pages | 881-92 |
| PubMed ID | 19246514 | Mgi Jnum | J:148522 |
| Mgi Id | MGI:3845467 | Doi | 10.1210/me.2008-0274 |
| Citation | Malakauskas SM, et al. (2009) Increased Insulin Sensitivity in Mice Lacking Collectrin, a Downstream Target of HNF-1{alpha}. Mol Endocrinol 23(6):881-892 |
| abstractText | Collectrin is a downstream target of the transcription factor HNF-1alpha, which is mutated in maturity-onset diabetes of the young subtype 3 (MODY3). Evidence from transgenic mouse models with collectrin over-expression in pancreatic islets suggests divergent roles for collectrin in influencing beta-cell mass and insulin exocytosis. To clarify the function of collectrin in the pancreas, we utilized a mouse line with targeted deletion of the gene. We examined pancreas morphology, glucose homeostasis by intraperitoneal glucose tolerance testing (IPGTT) and insulin tolerance testing (IPITT), and pancreas function by in vivo acute-phase insulin response determination and glucose-stimulated insulin secretion from isolated islets. We find no difference in either pancreas morphology or function between wild-type and collectrin-deficient animals (Tmem27(-/y)). However, we note that by 6 months of age Tmem27(-/y) mice exhibit increased insulin sensitivity by IPITT and decreased adiposity by DEXA scanning compared to wild-type. We have previously reported that Tmem27(-/y) mice exhibit profound aminoaciduria due to failed renal recovery. We now demonstrate that Tmem27(-/y) animals also display inappropriate excretion of some short-chain acylcarnitines derived from amino acid and fatty acid oxidation. We provide further evidence for compensatory upregulation of oxidative metabolism in Tmem27(-/y) mice, along with enhanced protein turnover associated with preserved lean mass even out to 1.5 years of age. Our studies suggest that collectrin-deficient mice activate a number of adaptive mechanisms to defend energy homeostasis in the setting of ongoing nutrient losses. |
