[HTML][HTML] Defective insulin secretory response to intravenous glucose in C57Bl/6J compared to C57Bl/6N mice

G Fergusson, M Éthier, M Guévremont, C Chrétien… - Molecular …, 2014 - Elsevier
G Fergusson, M Éthier, M Guévremont, C Chrétien, C Attané, E Joly, X Fioramonti, M Prentki
Molecular metabolism, 2014Elsevier
Abstract Objective The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic
research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt),
a mitochondrial enzyme involved in NADPH production, which has been suggested to lead
to glucose intolerance and beta-cell dysfunction. However, recent reports comparing Bl/6J to
Bl/6N (carrying the wild-type Nnt allele) under normal diet have led to conflicting results
using glucose tolerance tests. Thus, we assessed glucose-stimulated insulin secretion …
Objective
The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, recent reports comparing Bl/6J to Bl/6N (carrying the wild-type Nnt allele) under normal diet have led to conflicting results using glucose tolerance tests. Thus, we assessed glucose-stimulated insulin secretion (GSIS), insulin sensitivity, clearance and central glucose-induced insulin secretion in Bl/6J and N mice using gold-standard methodologies.
Methods
GSIS was measured using complementary tests (oral and intravenous glucose tolerance tests) and hyperglycemic clamps. Whole-body insulin sensitivity was assessed using euglycemic-hyperinsulinemic clamps. Neurally-mediated insulin secretion was measured during central hyperglycemia.
Results
Bl/6J mice have impaired GSIS compared to Bl/6N when glucose is administered intravenously during both a tolerance test and hyperglycemic clamp, but not in response to oral glucose. First and second phases of GSIS are altered without changes in whole body insulin sensitivity, insulin clearance, beta-cell mass or central response to glucose, thereby demonstrating defective beta-cell function in Bl/6J mice.
Conclusions
The Bl/6J mouse strain displays impaired insulin secretion. These results have important implications for choosing the appropriate test to assess beta-cell function and background strain in genetically modified mouse models.
Elsevier