Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Diabetic Medicine |
| Vol/bind | 22 |
| Udgave nummer | 1 |
| Sider (fra-til) | 74-80 |
| Antal sider | 6 |
| ISSN | 0742-3071 |
| DOI | |
| Status | Udgivet - 2005 |
Bibliografisk note
Keywords: Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Middle Aged; Mutation; Pedigree; Polymorphism, Single Nucleotide; Receptors, G-Protein-CoupledAdgang til dokumentet
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Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release. / Hamid, Y H; Vissing, H; Holst, B; Urhammer, S A; Pyke, C; Hansen, S K; Glümer, C; Borch-Johnsen, K; Jørgensen, T; Schwartz, T W; Pedersen, O; Hansen, T.
I: Diabetic Medicine, Bind 22, Nr. 1, 2005, s. 74-80.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release
AU - Hamid, Y H
AU - Vissing, H
AU - Holst, B
AU - Urhammer, S A
AU - Pyke, C
AU - Hansen, S K
AU - Glümer, C
AU - Borch-Johnsen, K
AU - Jørgensen, T
AU - Schwartz, T W
AU - Pedersen, O
AU - Hansen, T
N1 - Keywords: Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Middle Aged; Mutation; Pedigree; Polymorphism, Single Nucleotide; Receptors, G-Protein-Coupled
PY - 2005
Y1 - 2005
N2 - AIMS: Recently, a novel human G protein-coupled receptor 40 (GPR40), which is predominantly expressed in pancreatic islets, was shown to mediate an amplifying effect of long-chain fatty acids on glucose-induced insulin secretion. The present aim was to examine the coding region of GPR40 for variation and to assess whether identified variants confer an increased risk of Type 2 diabetes or altered insulin release. METHODS: Mutation analysis was performed in 43 patients with Type 2 diabetes, 18 normal glucose-tolerant subjects, and 3 maturity-onset of diabetes in the young (MODY) X patients using direct sequencing. Genotyping was performed using polymerase chain reaction (PCR)-generated primer extension products analysis by high throughput chip-based mass spectrometry (MALDI-TOF). The potential impact of GPR40 mutations on [(3)H]-myo-inositol turnover was estimated in COS-7 cells after stimulation with various concentrations of 5,8,11-eicosatriynoic acid. RESULTS: Two nucleotide substitutions, an Arg211His polymorphism and a rare Asp175Asn mutation, were identified. Both variants showed EC(50) values similar to the wild type. However, the maximal efficacy of the rare Asp175Asn was 39% lower compared with the wild type (P = 0.01). The Arg211His polymorphism had a similar allele frequency among 1384 Type 2 diabetic patients [MAF%; 23.4 (95% CI: 21.8-25.0)] and 4424 middle-aged glucose-tolerant subjects [24.1% (23.2-25.0)]. A genotype-quantitative trait study of 5597 non-diabetic, middle-aged subjects from the Inter99 cohort showed no significant differences in oral glucose tolerance test (OGTT)-derived estimates of insulin release between carriers of various GPR40 genotypes. CONCLUSIONS: Variations in the coding region of GPR40 do not appear to be associated with Type 2 diabetes or insulin release alterations.
AB - AIMS: Recently, a novel human G protein-coupled receptor 40 (GPR40), which is predominantly expressed in pancreatic islets, was shown to mediate an amplifying effect of long-chain fatty acids on glucose-induced insulin secretion. The present aim was to examine the coding region of GPR40 for variation and to assess whether identified variants confer an increased risk of Type 2 diabetes or altered insulin release. METHODS: Mutation analysis was performed in 43 patients with Type 2 diabetes, 18 normal glucose-tolerant subjects, and 3 maturity-onset of diabetes in the young (MODY) X patients using direct sequencing. Genotyping was performed using polymerase chain reaction (PCR)-generated primer extension products analysis by high throughput chip-based mass spectrometry (MALDI-TOF). The potential impact of GPR40 mutations on [(3)H]-myo-inositol turnover was estimated in COS-7 cells after stimulation with various concentrations of 5,8,11-eicosatriynoic acid. RESULTS: Two nucleotide substitutions, an Arg211His polymorphism and a rare Asp175Asn mutation, were identified. Both variants showed EC(50) values similar to the wild type. However, the maximal efficacy of the rare Asp175Asn was 39% lower compared with the wild type (P = 0.01). The Arg211His polymorphism had a similar allele frequency among 1384 Type 2 diabetic patients [MAF%; 23.4 (95% CI: 21.8-25.0)] and 4424 middle-aged glucose-tolerant subjects [24.1% (23.2-25.0)]. A genotype-quantitative trait study of 5597 non-diabetic, middle-aged subjects from the Inter99 cohort showed no significant differences in oral glucose tolerance test (OGTT)-derived estimates of insulin release between carriers of various GPR40 genotypes. CONCLUSIONS: Variations in the coding region of GPR40 do not appear to be associated with Type 2 diabetes or insulin release alterations.
U2 - 10.1111/j.1464-5491.2005.01505.x
DO - 10.1111/j.1464-5491.2005.01505.x
M3 - Journal article
C2 - 15606695
VL - 22
SP - 74
EP - 80
JO - Diabetic Medicine
JF - Diabetic Medicine
SN - 0742-3071
IS - 1
ER -