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Enhanced insulin sensitivity with loss of collectrin, an important mediator of renal amino acid recovery
Author(s) -
Malakauskas Sandra,
Kourany Wissam,
Lu Danhong,
Hohmeier Hans,
Newgard Christopher,
Le Thu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.947.13
Subject(s) - medicine , endocrinology , insulin , glucose homeostasis , mediator , pancreas , metabolic syndrome , amino acid , insulin resistance , homeostasis , biology , diabetes mellitus , type 2 diabetes , insulin sensitivity , biochemistry
The metabolic syndrome is a complex constellation of disorders which places patients at increased risk of diabetes, cardiovascular disease and all‐cause mortality. The objective of this study is to examine the metabolic effect of deletion of collectrin, a novel candidate mediator of the metabolic syndrome. We previously reported that targeted deletion of collectrin in the mouse results in failed recovery of filtered amino acids at the proximal tubule. We now report that collectrin‐deficient ( Tmem27 −/y ) mice develop enhanced insulin sensitivity with age. We observe a statistically significant decrease in blood glucose levels and a delayed hypoglycemic response during insulin tolerance testing (p 0.05). This enhanced insulin sensitivity is associated with a 25% decrease in adiposity by DEXA scanning (p=0.009), despite a 30% increase in food consumption, and persists with high‐fat feeding. Examination of the pancreas reveals no difference in morphometric variables, ‐cell proliferation by in vivo BrdU staining or glucose‐stimulated insulin secretion in isolated islets in Tmem27 −/y animals compared to wild‐type. This suggests that the enhanced insulin sensitivity does not arise from a difference in pancreatic physiology. We hypothesize that the increased insulin sensitivity associated with loss of collectrin results from altered amino acid flux in metabolic pathways important in energy homeostasis.