Measurement of the incretin hormones: glucagon-like peptide-1 and glucose-dependent insulinotropic peptide

https://doi.org/10.1016/j.jdiacomp.2014.12.006Get rights and content

Abstract

The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological methods.

Section snippets

The incretin hormones and type-2-diabetes

The gut hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are secreted in response to nutrient intake and play an essential role for postprandial glucose regulation by potentiating glucose-stimulated insulin secretion, a phenomenon called the incretin effect (Nauck, M.A. et al., 1986). In healthy humans, the effects of GIP and GLP-1 account for 25–70% of the total postprandial insulin response (depending on the size of the glucose load) (

Methods for hormone quantification

Incretin hormones circulate in low (picomolar) concentrations, meaning that assays must have high sensitivity. This can be provided using immune-based methods because it is possible to generate antibodies with equilibrium constants in the range of 1012 liters/mol, allowing reaction with femtomolar amounts of reagents (bioassays may have similar sensitivity, but often suffer from lack of specificity). Antibodies used in quantification assays are generally produced by immunization of animals with

Measurement of GLP-1

GLP-1 is a highly conserved peptide hormone (100% homology across species) encoded by the proglucagon gene (GCG), expressed by L-cells in the gut epithelium, certain neurons in the brain stem and by the pancreatic α-cell (Gu et al., 2013, Holst, 2007). The primary translation product of GCG is proglucagon, consisting of 160 amino acids, which is cleaved differentially according to tissue-specific expression of prohormone convertases (PC) 1/3 or PC2. Thus, in the L-cells, PC1/3 activity yields

Discussion

Reliable measurement of incretin hormones is not an easy task and should give rise to both theoretical and technical considerations. Common to all assays, the reliability of the measurements depends on 4 basic criteria, namely sensitivity, precision, specificity and accuracy (the Richterich criteria) (Bak et al., 2014b, Wewer Albrechtsen et al., 2014b). As already discussed, sensitivity may present a definite problem since circulating concentrations may be very low, particularly of intact

References (42)

  • M.J. Bak

    Specificity and sensitivity of commercially available assays for glucagon-like peptide-1 (GLP-1): Implications for GLP-1 measurements in clinical studies

    Diabetes, Obesity & Metabolism

    (2014)
  • F.G. Baldissera et al.

    Glicentin 1–61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs

    Diabetologia

    (1986)
  • S.A. Berson

    Insulin-I131 metabolism in human subjects: Demonstration of insulin binding globulin in the circulation of insulin treated subjects

    The Journal of Clinical Investigation

    (1956)
  • D. Bousquet-Moore

    Reversal of physiological deficits caused by diminished levels of peptidylglycine α-amidating monooxygenase by dietary copper

    Endocrinology

    (2009)
  • A.M. Buchan

    Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man

    Histochemistry

    (1978)
  • J. Cox et al.

    MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification

    Nature Biotechnology

    (2008)
  • W. Creutzfeldt

    The incretin concept today

    Diabetologia

    (1979)
  • C.F. Deacon et al.

    Physiology of incretins in health and disease

    The Review of Diabetic Studies: RDS

    (2011)
  • C.F. Deacon

    Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig

    The American Journal of Physiology

    (1996)
  • C.F. Deacon et al.

    Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide

    The Journal of Clinical Endocrinology and Metabolism

    (2000)
  • H. Elrick

    Plasma insulin response to oral and intravenous glucose administration

    The Journal of Clinical Endocrinology and Metabolism

    (1964)
  • Cited by (0)

    Declaration of interest: The authors declare no financial or otherwise conflicts of interest that may have influenced the preparation of this review.

    1

    Contributed equally to preparation of this manuscript.

    View full text