Measurement of the incretin hormones: glucagon-like peptide-1 and glucose-dependent insulinotropic peptide
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)
- et al.
Immunoassays for the incretin hormones GIP and GLP-1
Best Practice & Research. Clinical Endocrinology & Metabolism
(2009) - et al.
Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G
Immunochemistry
(1971) Proglucagon processing in porcine and human pancreas
Journal of Biological Chemistry
(1994)Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7–36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides
Regulatory Peptides
(1995)- et al.
The heterogeneity of gastric inhibitory polypeptide in porcine and human gastrointestinal mucosa evaluated with five different antisera
Regulatory Peptides
(1984) GLP-1 amidation efficiency along the length of the intestine in mice, rats and pigs and in GLP-1 secreting cell lines
Peptides
(2014)- et al.
Glucagon-related peptide 1 (GLP-1): Hormone and neurotransmitter
Regulatory Peptides
(2005) GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine
Regulatory Peptides
(2003)Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor
The Journal of Biological Chemistry
(2006)Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans
European Journal of Endocrinology/European Federation of Endocrine Societies
(2014)
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
Glicentin 1–61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs
Diabetologia
Insulin-I131 metabolism in human subjects: Demonstration of insulin binding globulin in the circulation of insulin treated subjects
The Journal of Clinical Investigation
Reversal of physiological deficits caused by diminished levels of peptidylglycine α-amidating monooxygenase by dietary copper
Endocrinology
Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man
Histochemistry
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification
Nature Biotechnology
The incretin concept today
Diabetologia
Physiology of incretins in health and disease
The Review of Diabetic Studies: RDS
Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig
The American Journal of Physiology
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
Plasma insulin response to oral and intravenous glucose administration
The Journal of Clinical Endocrinology and Metabolism
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Declaration of interest: The authors declare no financial or otherwise conflicts of interest that may have influenced the preparation of this review.
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Contributed equally to preparation of this manuscript.