Typical Danish Caucasian type 2 diabetic patients do not commonly carry genetic variants in GIP and GLP-1 encoding regions of the proGIP and proglucagon genes.
BACKGROUND
The enteroinsular-axis is abnormal in type 2 diabetics, which contributes to the diabetic phenotype. The effect of the incretin hormone gastric inhibitory polypeptide (GIP) and the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) are thus greatly diminished. The explanation for these changes could be changes in the structure of either of the hormones or their receptors. Thus, the aim of this study was to study the occurrence of genetic variants in the GIP and GLP-1 encoding regions of the proGIP and proglucagon genes in type 2 diabetic patients and matched control subjects.


RESULTS
Genomic DNA was extracted from buffy coats from 12 Caucasian type 2 diabetics and 12 healthy subjects, matched with respect to sex, age and BMI. The GIP and GLP-1 sequences were amplified using specific primers using the polymerase chain reaction (PCR). The amplified products were then sequenced. No germ-line mutations were identified in the GIP and the GLP-1 encoding regions of the proGIP and proglucagon genes in either the type 2 diabetic or the control subjects.


CONCLUSIONS
The perturbed incretin effect in type 2 diabetics is not commonly caused by genetic variants in either the GIP or the GLP-1 encoding genes in type 2 diabetics.
Ørskov
Cathrine
C
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, Copenhagen DK 2200, Denmark. c.orskov@mai.ku.dk
Hjorth
Siv A
SA
Jensen
Anne D
AD
Vilsbøll
Tina
T
D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism; D017422:Sequence Analysis, DNA; D044465:White People
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D004247:DNA; D005934:Glucagon; C041086:gastric inhibitory polypeptide receptor