Insulin secretory response in conscious FVB/NJ and DBA/2J mice

Transgenic mice are a valuable tool to study diabetes and other disorders. Phenotypes often differ based on the genetic background of the mutant mouse. Here we use the hyperglycemic clamp technique in chronically catheterized 11‐week old male FVB/NJ (n=9) and DBA/2J (n=7) mice to assess the insulin response to a fixed hyperglycemic stimulus. A 120 min hyperglycemic clamp was performed 5 days after surgical implantation of carotid artery (sampling) and jugular vein (infusing) catheters. Five hour fasted mice were infused with glucose to achieve steady state blood glucose (mg/dL) of 250–300 from 80 to120 min. Basal FVB/NJ blood glucose, insulin (mU/mL), and c‐peptide (ng/mL) were 174±8, 18.1±3.9, and 1.1±0.2. A GIR (mg/kg/min) of 19.8±5.4 was required to clamp FVB/NJ blood glucose at 280±25. Despite the hyperglycemic stimulus, insulin (18.3±3.4) and c‐peptide (1.2±0.1) did not increase in FVB/NJ mice. Basal DBA/2J blood glucose, insulin, and c‐peptide were 140±9, 25.4±5.6, and 1.4±0.2. A GIR of 33.6±7.3 was required to clamp DBA/2J blood glucose at 252±8. At steady state, insulin (58.9±13.4) and c‐peptide (2.7±0.5) were both markedly increased above basal levels. In summary, FVB/NJ mice have elevated fasting glucose and an impaired insulin response to hyperglycemia in comparison to DBA/2J mice. These strain differences are important to consider when interpreting the phenotype of genetic mutants affecting islet function. Research supported by NIH DK50277 and DK59637.