A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility

Background Characterization of beta-cell function in humans is essential fo r identifying genetic defects involved in abnormal insulin secretion and th e pathogenesis of type 2 diabetes. Materials and methods We designed a novel test assessing plasma insulin and C-peptide in response to 3 different secretagogues. Seven lean, healthy vo lunteers twice underwent a 200 min hyperglycaemic clamp (10 mmol L-1) with administration of GLP-1 (1.5 pmol . kg(-1) . min(-1)) starting at 120 min a nd an arginine bolus at 180 min. We determined glucose-induced first and se cond-phase insulin secretion, GLP-1-stimulated insulin secretion, arginine- stimulated insulin response (increase above prestimulus, Delta I-arg) and t he maximal, i.e. highest absolute, insulin concentration (I-max). Insulin s ensitivity was assessed during second-phase hyperglycaemia. On a third occa sion 6 subjects additionally received an arginine bolus at > 25 mm blood gl ucose, a test hitherto claimed to provoke maximal insulin secretion. Results Insulin levels increased from 46 +/- 11 pm to 566 +/- 202 pm at 120 min, to 5104 +/- 1179 pm at 180 min and to maximally 8361 +/- 1368 pm afte r arginine (all P < 0.001). The within subject coefficients of variation of the different secretion parameters ranged from 10 +/- 3% to 16 +/- 6%. Exc ept for second-phase which failed to correlate significantly with Delta I-a rg (r = 0.52, P = 0.23) and I-max (r = 0.75, P = 0.053) all phases of insul in secretion correlated with one another. The insulin concentration after t he arginine bolus at > 25 mm glucose (n = 6) was 2773 +/- 855 pm vs. 7562 /- 1168 pm for I-max (P = 0.003). Conclusion This novel insulin secretion test elicits a distinct pattern of plasma insulin concentrations in response to the secretagogues glucose, GLP -1 and arginine and is highly reproducible and can be used for differential characterization of islet function.