The blood concentration of intact
proinsulin, but not total
proinsulin, has been suggested to be a diagnostic marker for
type 2 diabetes mellitus (T2DM), but a sensitive assay specific for rodent intact
proinsulin is lacking. Here, a novel
enzyme-linked
immunosorbent assay (ELISA) for mouse intact
proinsulin was developed. The developed ELISA detected mouse intact
proinsulin with the working range of 8.3 to 2700pg/ml. Cross-reactivity with mouse split-32,33
proinsulin was approximately 100times lower than the reactivity with mouse intact
proinsulin, and no cross-reactivity with mouse
insulin was detected. The developed ELISA was sufficiently sensitive to detect low levels of intact
proinsulin in normal mouse plasma. The measurement by the developed ELISA revealed that intact
proinsulin was elevated in the plasma of type 2 diabetic db/db mice as mice aged, and the ratio of intact
proinsulin/
insulin in plasma was correlated with levels of
glycated hemoglobin A1c as seen in T2DM patients. These results suggest that the plasma level of intact
proinsulin, but not total
proinsulin, is a sensitive marker for pancreatic dysfunction and the ensuring diabetic
disease progression of db/db mice. This ELISA could aid nonclinical evaluation of therapeutic interventions in T2DM.