Hyperinsulinemia decreases second-phase but not first-phase arginine- induced insulin release in humans

P. M. Piatti, A. E. Pontiroli, A. Caumo, G. Santambrogio, L. D. Monti, S. Costa, F. Garbetta, L. Baruffaldi, C. Cobelli, G. Pozza

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Abstract

The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU · kg -1 · min -1) and a high-dose (1.20 mU · kg -1 · min -1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means ± SE) 60.0 ± 2.4, 165.6 ± 1.8, and 455.4 ± 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C- peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 ± 10.1, 73.7 ± 12.8, and 73.4 ± 10.3 pmol/kg, whereas second phase was 266.1 ± 46.0, 143.1 ± 33.5, and 133.0 ± 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively. We conclude that second-phase, but not first-phase, arginine-induced insulin release is modulated by the pre-stimulus insulin levels. In addition, the inhibitory effect exerted by insulin on second-phase insulin response to arginine appears to be maximized at insulin levels only four times basal.

Original languageEnglish
Pages (from-to)1157-1163
Number of pages7
JournalDiabetes
Volume43
Issue number9
Publication statusPublished - 1994

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Hyperinsulinism
Arginine
Insulin
C-Peptide
Glucose Clamp Technique

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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Hyperinsulinemia decreases second-phase but not first-phase arginine- induced insulin release in humans. / Piatti, P. M.; Pontiroli, A. E.; Caumo, A.; Santambrogio, G.; Monti, L. D.; Costa, S.; Garbetta, F.; Baruffaldi, L.; Cobelli, C.; Pozza, G.

In: Diabetes, Vol. 43, No. 9, 1994, p. 1157-1163.

Research output: Contribution to journalArticle

Piatti, PM, Pontiroli, AE, Caumo, A, Santambrogio, G, Monti, LD, Costa, S, Garbetta, F, Baruffaldi, L, Cobelli, C & Pozza, G 1994, 'Hyperinsulinemia decreases second-phase but not first-phase arginine- induced insulin release in humans', Diabetes, vol. 43, no. 9, pp. 1157-1163.
Piatti, P. M. ; Pontiroli, A. E. ; Caumo, A. ; Santambrogio, G. ; Monti, L. D. ; Costa, S. ; Garbetta, F. ; Baruffaldi, L. ; Cobelli, C. ; Pozza, G. / Hyperinsulinemia decreases second-phase but not first-phase arginine- induced insulin release in humans. In: Diabetes. 1994 ; Vol. 43, No. 9. pp. 1157-1163.
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T1 - Hyperinsulinemia decreases second-phase but not first-phase arginine- induced insulin release in humans

AU - Piatti, P. M.

AU - Pontiroli, A. E.

AU - Caumo, A.

AU - Santambrogio, G.

AU - Monti, L. D.

AU - Costa, S.

AU - Garbetta, F.

AU - Baruffaldi, L.

AU - Cobelli, C.

AU - Pozza, G.

PY - 1994

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N2 - The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU · kg -1 · min -1) and a high-dose (1.20 mU · kg -1 · min -1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means ± SE) 60.0 ± 2.4, 165.6 ± 1.8, and 455.4 ± 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C- peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 ± 10.1, 73.7 ± 12.8, and 73.4 ± 10.3 pmol/kg, whereas second phase was 266.1 ± 46.0, 143.1 ± 33.5, and 133.0 ± 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively. We conclude that second-phase, but not first-phase, arginine-induced insulin release is modulated by the pre-stimulus insulin levels. In addition, the inhibitory effect exerted by insulin on second-phase insulin response to arginine appears to be maximized at insulin levels only four times basal.

AB - The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU · kg -1 · min -1) and a high-dose (1.20 mU · kg -1 · min -1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means ± SE) 60.0 ± 2.4, 165.6 ± 1.8, and 455.4 ± 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C- peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 ± 10.1, 73.7 ± 12.8, and 73.4 ± 10.3 pmol/kg, whereas second phase was 266.1 ± 46.0, 143.1 ± 33.5, and 133.0 ± 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively. We conclude that second-phase, but not first-phase, arginine-induced insulin release is modulated by the pre-stimulus insulin levels. In addition, the inhibitory effect exerted by insulin on second-phase insulin response to arginine appears to be maximized at insulin levels only four times basal.

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