Clarification: Are C57BL/6J Male Mice Really Glucose Intolerant?

JAX® NOTES Issue 504, Winter 2006

Many of our customers use C57BL/6J (B6, 000664) mice as normoglycemic and glucose tolerant controls for certain obesity/diabesity and genetically engineered mouse mutants with a B6 background. We therefore wish to clarify a potentially confusing article in the last issue of JAX® NOTES (JAX® NOTES 2006). The article reported that United Kingdom researchers (Freeman et al. 2006) demonstrated that a spontaneous mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene partly explains why, in response to a bolus injection of glucose, B6 males secrete less insulin and clear glucose more slowly than do C3H/HeJ males. Although B6 males fed a chow diet clear glucose slower over a two-hour span than do certain other strains (Goren et al. 2004), they clear it much faster than do males from truly glucose-intolerant strains, such as KK/HlJ (002106), NZO/HlLtJ (002105), and NON/LtJ (002423), the latter reportedly expressing the wild-type Nnt allele (online supplement to Freeman et al. 2006). The Mouse Phenome Database indicates that though plasma glucose levels in B6 mice before and after being fed a high fat diet are higher than those in many other comparably fed inbred strains, they are within the normal range for inbred strains. Thus, as applied to B6 mice, glucose intolerance is a relative term: due to diminished glucose-stimulated insulin secretion, B6 clearance rates for injected glucose are slower than for some inbred strains. However, B6 males are very insulin sensitive and, following a glucose injection, restore their glucose levels to within a normal range over a two-hour period.

References

Freeman HC, Hugill A, Dear NT, Ashcroft FM, Cox RD. 2006. Deletion of nicotinamide nucleotide transhydrogenase: a new quantitive trait locus accounting for glucose intolerance in C57BL/6J mice. Diabetes 55:2153-6.

Goren JH, Kulkarni RN, Kahn CR. 2004. Glucose Homeostasis and Tissue Transcript Content of Insulin Signaling Intermediates in Four Inbred Strains of Mice: C57BL/6, C57BLKS/6, DBA/2, and 129X1. Endocrinology 145:3307-23

JAX® NOTES. 2006. Cause of glucose intolerance in C57BL/6J mice discovered. JAX® NOTES 403:7.