Glucose metabolism in vivo in four commonly used inbred mouse strains.
OBJECTIVE
To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains.


METHODS
Hyperinsulinemic-euglycemic (approximately 8.5 mmol/l) and -hypoglycemic (approximately 3.0 mmol/l) clamps were done in catheterized, 5-h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (approximately 15 mmol/l) were done to assess insulin secretion and compared with results in perifused islets.


RESULTS
Insulin action and hypoglycemic counter-regulatory and insulin secretory phenotypes varied considerably in four inbred mouse strains. In vivo insulin secretion was greatest in 129X1/Sv mice, but the counter-regulatory response to hypoglycemia was blunted. FVB/N mice in vivo showed no increase in glucose-stimulated insulin secretion, relative hepatic insulin resistance, and the highest counter-regulatory response to hypoglycemia. In DBA/2 mice, insulin action was lowest among the strains, and islets isolated had the greatest glucose-stimulated insulin secretion in vitro. In C57BL/6 mice, in vivo physiological responses to hyperinsulinemia at euglycemia and hypoglycemia were intermediate relative to other strains. Insulin secretion by C57BL/6 mice was similar to that in other strains in contrast to the blunted glucose-stimulated insulin secretion from isolated islets.


CONCLUSIONS
Strain-dependent differences exist in four inbred mouse strains frequently used for genetic manipulation and study of glucose metabolism. These results are important for selecting inbred mice to study glucose metabolism and for interpreting and designing experiments.
Berglund
Eric D
ED
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. eric.d.berglund@vanderbilt.edu
Li
Candice Y
CY
Poffenberger
Greg
G
Ayala
Julio E
JE
Fueger
Patrick T
PT
Willis
Shannon E
SE
Jewell
Marybeth M
MM
Powers
Alvin C
AC
Wasserman
David H
DH
D000818:Animals; D030801:Animals, Genetically Modified; D000830:Animals, Laboratory; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000378:metabolism*; D013045:Species Specificity
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose