A Novel Hyperglycaemic Clamp for Characterization of Islet Function in Humans: Assessment of Three Different Secretagogues, Maximal Insulin Response and Reproducibility

Eur J Clin Invest. 2000 May;30(5):411-8. doi: 10.1046/j.1365-2362.2000.00649.x.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / administration & dosage
  • Arginine / adverse effects
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucagon / administration & dosage
  • Glucagon / adverse effects
  • Glucagon / blood
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Glucose / administration & dosage
  • Glucose Clamp Technique / adverse effects
  • Glucose Clamp Technique / standards*
  • Humans
  • Hyperglycemia / diagnosis
  • Hyperglycemia / metabolism*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / adverse effects
  • Peptide Fragments / metabolism
  • Protein Precursors / administration & dosage
  • Protein Precursors / adverse effects
  • Reproducibility of Results

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Arginine
  • Glucose