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Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects.
- Source :
-
Diabetes [Diabetes] 1996 Dec; Vol. 45 (12), pp. 1701-5. - Publication Year :
- 1996
-
Abstract
- Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We have identified two missense mutations, Gly198-->Cys (Gly198Cys) in exon 7 and Glu354-->Gln (Glu354Gln) in exon 12. Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. Association studies show no relationship between NIDDM and either of the two mutations.
- Subjects :
- Alleles
Animals
CHO Cells
Cricetinae
Cyclic AMP metabolism
DNA Primers
Gastric Inhibitory Polypeptide pharmacology
Humans
Insulin metabolism
Insulin Secretion
Japan
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Receptors, Gastrointestinal Hormone physiology
Structure-Activity Relationship
DNA Mutational Analysis
Diabetes Mellitus, Type 2 genetics
Mutation
Receptors, Gastrointestinal Hormone genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0012-1797
- Volume :
- 45
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 8922354
- Full Text :
- https://doi.org/10.2337/diab.45.12.1701