BACKGROUND: Characterization of beta-cell function in humans is essential for identifying genetic defects involved in abnormal insulin secretion and the 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 volunteers 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 and an arginine bolus at 180 min. We determined glucose-induced first and second-phase insulin secretion, GLP-1-stimulated insulin secretion, arginine-stimulated insulin response (increase above prestimulus, DeltaIarg) and the maximal, i. e. highest absolute, insulin concentration (Imax). Insulin sensitivity was assessed during second-phase hyperglycaemia. On a third occasion 6 subjects additionally received an arginine bolus at > 25 mM blood glucose, 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 after arginine (all P < 0.001). The within subject coefficients of variation of the different secretion parameters ranged from 10 +/- 3% to 16 +/- 6%. Except for second-phase which failed to correlate significantly with DeltaIarg (r = 0.52, P = 0.23) and Imax (r = 0.75, P = 0.053) all phases of insulin secretion correlated with one another. The insulin concentration after the arginine bolus at > 25 mM glucose (n = 6) was 2773 +/- 855 pM vs. 7562 +/- 1168 pM for Imax (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.
BACKGROUND: Characterization of beta-cell function in humans is essential for identifying genetic defects involved in abnormal insulin secretion and the 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 volunteers 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 and an arginine bolus at 180 min. We determined glucose-induced first and second-phase insulin secretion, GLP-1-stimulated insulin secretion, arginine-stimulated insulin response (increase above prestimulus, DeltaIarg) and the maximal, i. e. highest absolute, insulin concentration (Imax). Insulin sensitivity was assessed during second-phase hyperglycaemia. On a third occasion 6 subjects additionally received an arginine bolus at > 25 mM blood glucose, 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 after arginine (all P < 0.001). The within subject coefficients of variation of the different secretion parameters ranged from 10 +/- 3% to 16 +/- 6%. Except for second-phase which failed to correlate significantly with DeltaIarg (r = 0.52, P = 0.23) and Imax (r = 0.75, P = 0.053) all phases of insulin secretion correlated with one another. The insulin concentration after the arginine bolus at > 25 mM glucose (n = 6) was 2773 +/- 855 pM vs. 7562 +/- 1168 pM for Imax (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.
Authors: M Berkelaar; E M W Eekhoff; A M C Simonis-Bik; D I Boomsma; M Diamant; R G Ijzerman; J M Dekker; L M 't Hart; E J C de Geus Journal: Diabetologia Date: 2013-02-13 Impact factor: 10.122
Authors: A M C Simonis-Bik; E M W Eekhoff; M H M de Moor; M H H Kramer; D I Boomsma; R J Heine; J M Dekker; J A Maassen; L M 't Hart; M Diamant; E J C de Geus Journal: Diabetologia Date: 2009-10-03 Impact factor: 10.122
Authors: S A Schäfer; K Müssig; H Staiger; F Machicao; N Stefan; B Gallwitz; H U Häring; A Fritsche Journal: Diabetologia Date: 2009-03-28 Impact factor: 10.122
Authors: Felicia Gerst; Benjamin A Jaghutriz; Harald Staiger; Anke M Schulte; Estela Lorza-Gil; Gabriele Kaiser; Madhura Panse; Sieglinde Haug; Martin Heni; Monika Schütz; Mandy Stadion; Annette Schürmann; Flavia Marzetta; Mark Ibberson; Bence Sipos; Falko Fend; Thomas Fleming; Peter P Nawroth; Alfred Königsrainer; Silvio Nadalin; Silvia Wagner; Andreas Peter; Andreas Fritsche; Daniela Richter; Michele Solimena; Hans-Ulrich Häring; Susanne Ullrich; Robert Wagner Journal: J Clin Endocrinol Metab Date: 2018-12-01 Impact factor: 5.958
Authors: Annemarie M Simonis-Bik; Giel Nijpels; Timon W van Haeften; Jeanine J Houwing-Duistermaat; Dorret I Boomsma; Erwin Reiling; Els C van Hove; Michaela Diamant; Mark H H Kramer; Robert J Heine; J Antonie Maassen; P Eline Slagboom; Gonneke Willemsen; Jacqueline M Dekker; Elisabeth M Eekhoff; Eco J de Geus; Leen M 't Hart Journal: Diabetes Date: 2009-10-15 Impact factor: 9.461
Authors: Leen M 't Hart; Annemarie M Simonis-Bik; Giel Nijpels; Timon W van Haeften; Silke A Schäfer; Jeanine J Houwing-Duistermaat; Dorret I Boomsma; Marlous J Groenewoud; Erwin Reiling; Els C van Hove; Michaela Diamant; Mark H H Kramer; Robert J Heine; J Antonie Maassen; Kerstin Kirchhoff; Fausto Machicao; Hans-Ulrich Häring; P Eline Slagboom; Gonneke Willemsen; Elisabeth M Eekhoff; Eco J de Geus; Jacqueline M Dekker; Andreas Fritsche Journal: Diabetes Date: 2009-10-06 Impact factor: 9.461