Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release

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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.

In: Diabetic Medicine, Vol. 22, No. 1, 2005, p. 74-80.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hamid, YH, Vissing, H, Holst, B, Urhammer, SA, Pyke, C, Hansen, SK, Glümer, C, Borch-Johnsen, K, Jørgensen, T, Schwartz, TW, Pedersen, O & Hansen, T 2005, 'Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release', Diabetic Medicine, vol. 22, no. 1, pp. 74-80. https://doi.org/10.1111/j.1464-5491.2005.01505.x

APA

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. (2005). Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release. Diabetic Medicine, 22(1), 74-80. https://doi.org/10.1111/j.1464-5491.2005.01505.x

Vancouver

Hamid YH, Vissing H, Holst B, Urhammer SA, Pyke C, Hansen SK et al. Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release. Diabetic Medicine. 2005;22(1):74-80. https://doi.org/10.1111/j.1464-5491.2005.01505.x

Author

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. / Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release. In: Diabetic Medicine. 2005 ; Vol. 22, No. 1. pp. 74-80.

Bibtex

@article{62d7ad30fad611ddb219000ea68e967b,
title = "Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release",
abstract = "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.",
author = "Hamid, {Y H} and H Vissing and B Holst and Urhammer, {S A} and C Pyke and Hansen, {S K} and C Gl{\"u}mer and K Borch-Johnsen and T J{\o}rgensen and Schwartz, {T W} and O Pedersen and T Hansen",
note = "Keywords: Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Middle Aged; Mutation; Pedigree; Polymorphism, Single Nucleotide; Receptors, G-Protein-Coupled",
year = "2005",
doi = "10.1111/j.1464-5491.2005.01505.x",
language = "English",
volume = "22",
pages = "74--80",
journal = "Diabetic Medicine",
issn = "0742-3071",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

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 -

ID: 10536252