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Molecular and Cellular Biology, August 2005, p. 6570-6577, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6570-6577.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Abnormal Glucose Homeostasis and Pancreatic Islet Function in Mice with Inactivation of the Fem1b Gene

Deyin Lu,1,2 Tereza Ventura-Holman,1,2 Jing Li,1,2 Robert W. McMurray,2 Jose S. Subauste,1,2 and Joseph F. Maher1,2*

G.V. (Sonny) Montgomery Veterans Affairs Medical Center,1 Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi2

Received 5 November 2004/ Returned for modification 21 January 2005/ Accepted 1 May 2005

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 ß cells and non-ß cells, and is highly expressed in INS-1E cells, a pancreatic ß-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.

* Corresponding author. Mailing address: Veterans Affairs Medical Center-Research Svc. (151), 1500 E. Woodrow Wilson Blvd., Jackson, MS 39216. Phone: (601) 362-4471, ext. 1117. Fax: (601) 364-1390. E-mail: joseph.maher{at}med.va.gov.

Molecular and Cellular Biology, August 2005, p. 6570-6577, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6570-6577.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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