Abnormal glucose homeostasis and pancreatic islet function in mice with inactivation of the Fem1b gene.
Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively. Here, we have developed Fem1b knockout (Fem1b-KO) mice, with targeted inactivation of Fem1b, a homolog of the nematode fem-1 sex determination gene. We show that the Fem1b-KO mice display abnormal glucose tolerance and that this is due predominantly to defective glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion is also affected. The Fem1b gene is expressed in pancreatic islets, within both beta cells and non-beta cells, and is highly expressed in INS-1E cells, a pancreatic beta-cell line. In conclusion, these data implicate Fem1b in pancreatic islet function and insulin secretion, strengthening evidence that a genetic pathway homologous to nematode sex determination may be involved in glucose homeostasis and suggesting novel genes and processes as potential candidates in the pathogenesis of diabetes mellitus.
Lu
Deyin
D
Veterans Affairs Medical Center-Research Svc. (151), 1500 E. Woodrow Wilson Blvd., Jackson, MS 39216, USA.
Ventura-Holman
Tereza
T
Li
Jing
J
McMurray
Robert W
RW
Subauste
Jose S
JS
Maher
Joseph F
JF
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology*; D005947:Glucose / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C403492:FEM1B protein, human; C498596:Fem1b protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes; D005947:Glucose