Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • P Weyrich
  • F Machicao
  • H Staiger
  • P Simon
  • C Thamer
  • J Machann
  • F Schick
  • A Guirguis
  • A Fritsche
  • N Stefan
  • H-U Haering
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000249299600011&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1007/s00125-007-0788-8
eISSN
1432-0428
Externe Identifier
  • Clarivate Analytics Document Solution ID: 208DI
  • PubMed Identifier: 17701023
ISSN
0012-186X
Ausgabe der Veröffentlichung
10
Zeitschrift
DIABETOLOGIA
Schlüsselwörter
  • AMPK
  • AMP protein kinase
  • insulin resistance
  • LDL-cholesterol
  • PRKAG3
  • single nucleotide polymorphism
  • SNP
  • type 2 diabetes mellitus
Paginierung
2097 - 2106
Datum der Veröffentlichung
2007
Status
Published
Titel
Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites
Sub types
  • Article
Ausgabe der Zeitschrift
50

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • P Weyrich
  • F Machicao
  • H Staiger
  • P Simon
  • C Thamer
  • J Machann
  • F Schick
  • A Guirguis
  • A Fritsche
  • N Stefan
  • H-U Häring
DOI
10.1007/s00125-007-0788-8
eISSN
1432-0428
ISSN
0012-186X
Ausgabe der Veröffentlichung
10
Zeitschrift
Diabetologia
Sprache
en
Online publication date
2007
Paginierung
2097 - 2106
Datum der Veröffentlichung
2007
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s00125-007-0788-8
Datum der Datenerfassung
2021
Titel
Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites
Ausgabe der Zeitschrift
50

Datenquelle: Crossref

Abstract
<h4>Aims/hypothesis</h4>AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that acts as an intracellular fuel sensor, directing multiple metabolic pathways in a catabolic direction in times of nutrient shortage. In humans, three different gamma-subunits (gamma(1), gamma(2), gamma(3)) have been identified as AMPK regulators. The AMPKgamma3 (protein kinase, AMP-activated, gamma 3 non-catalytic subunit, PRKAG3) isoform plays a role in gene regulation in glucose/lipid metabolism and skeletal muscle glycogen content. We investigated whether PRKAG3, in addition to being expressed in skeletal muscle, is also expressed in human liver. We also investigated whether genetic variance in PRKAG3 is associated with glucose and/or lipid metabolism in non-diabetic whites.<h4>Materials and methods</h4>After sequencing a screening cohort (n = 50) in the PRKAG3 locus, we genotyped 1061 participants for frequently found single nucleotide polymorphisms (SNPs). Association analyses between genotypes/haplotypes and metabolic traits were carried out.<h4>Results</h4>We detected PRKAG3 expression in human liver and skeletal muscle. Two SNPs (rs692243, rs6436094) with minor allele frequencies of 0.16 and 0.26 respectively and in moderate linkage disequilibrium (D' = 0.92; r (2) = 0.47) were found. rs692243 (C/G) confers a Pro71Ala mutation, while rs6436094 (A/G) is located in the 3' untranslated region. No associations with prediabetic traits such as body fat distribution, insulin resistance or insulin secretion were found (p > 0.15 for all). However, the minor alleles of both SNPs were significantly associated with higher serum LDL-cholesterol and apolipoprotein (Apo) B-100 levels (rs692243: CG:LDL 4.3%, ApoB-100 3.4%; GG:LDL 7.6%, ApoB-100 5.4%; p = 0.008 and p = 0.01 respectively; rs6436094: AG:LDL 3.3%, ApoB-100 1.7%; GG:LDL 11.3%, ApoB-100 11.1%; p = 0.009 and p = 0.05 respectively; dominant model). The GG/GG diplotype homozygous for both minor SNP alleles displayed the highest LDL-cholesterol among all frequent diplotypes (p = 0.059).<h4>Conclusions/interpretation</h4>While genetic variability in PRKAG3 does not seem to have a major effect on glucose metabolism, it may play an important role in lipoprotein metabolism in humans.
Addresses
  • Department of Internal Medicine, Division of Endocrinology, Metabolism, Pathobiochemistry and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
Autoren
  • P Weyrich
  • F Machicao
  • H Staiger
  • P Simon
  • C Thamer
  • J Machann
  • F Schick
  • A Guirguis
  • A Fritsche
  • N Stefan
  • H-U Häring
DOI
10.1007/s00125-007-0788-8
eISSN
1432-0428
Externe Identifier
  • PubMed Identifier: 17701023
Open access
false
ISSN
0012-186X
Ausgabe der Veröffentlichung
10
Zeitschrift
Diabetologia
Schlüsselwörter
  • Liver
  • Humans
  • Multienzyme Complexes
  • Insulin
  • Glucose
  • Blood Glucose
  • Lipids
  • Lipoproteins
  • Protein Subunits
  • DNA, Complementary
  • Glucose Tolerance Test
  • Cloning, Molecular
  • Reverse Transcriptase Polymerase Chain Reaction
  • Genotype
  • Genetic Variation
  • AMP-Activated Protein Kinases
  • Insulin Secretion
  • Protein Serine-Threonine Kinases
  • White People
Sprache
eng
Medium
Print-Electronic
Online publication date
2007
Paginierung
2097 - 2106
Datum der Veröffentlichung
2007
Status
Published
Datum der Datenerfassung
2007
Titel
Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
50

Datenquelle: Europe PubMed Central

Abstract
AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that acts as an intracellular fuel sensor, directing multiple metabolic pathways in a catabolic direction in times of nutrient shortage. In humans, three different gamma-subunits (gamma(1), gamma(2), gamma(3)) have been identified as AMPK regulators. The AMPKgamma3 (protein kinase, AMP-activated, gamma 3 non-catalytic subunit, PRKAG3) isoform plays a role in gene regulation in glucose/lipid metabolism and skeletal muscle glycogen content. We investigated whether PRKAG3, in addition to being expressed in skeletal muscle, is also expressed in human liver. We also investigated whether genetic variance in PRKAG3 is associated with glucose and/or lipid metabolism in non-diabetic whites. MATERIALS AND METHODS: After sequencing a screening cohort (n = 50) in the PRKAG3 locus, we genotyped 1061 participants for frequently found single nucleotide polymorphisms (SNPs). Association analyses between genotypes/haplotypes and metabolic traits were carried out. RESULTS: We detected PRKAG3 expression in human liver and skeletal muscle. Two SNPs (rs692243, rs6436094) with minor allele frequencies of 0.16 and 0.26 respectively and in moderate linkage disequilibrium (D' = 0.92; r (2) = 0.47) were found. rs692243 (C/G) confers a Pro71Ala mutation, while rs6436094 (A/G) is located in the 3' untranslated region. No associations with prediabetic traits such as body fat distribution, insulin resistance or insulin secretion were found (p > 0.15 for all). However, the minor alleles of both SNPs were significantly associated with higher serum LDL-cholesterol and apolipoprotein (Apo) B-100 levels (rs692243: CG:LDL 4.3%, ApoB-100 3.4%; GG:LDL 7.6%, ApoB-100 5.4%; p = 0.008 and p = 0.01 respectively; rs6436094: AG:LDL 3.3%, ApoB-100 1.7%; GG:LDL 11.3%, ApoB-100 11.1%; p = 0.009 and p = 0.05 respectively; dominant model). The GG/GG diplotype homozygous for both minor SNP alleles displayed the highest LDL-cholesterol among all frequent diplotypes (p = 0.059). CONCLUSIONS/INTERPRETATION: While genetic variability in PRKAG3 does not seem to have a major effect on glucose metabolism, it may play an important role in lipoprotein metabolism in humans.
Date of acceptance
2007
Autoren
  • P Weyrich
  • F Machicao
  • H Staiger
  • P Simon
  • C Thamer
  • J Machann
  • F Schick
  • A Guirguis
  • A Fritsche
  • N Stefan
  • H-U Häring
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17701023
DOI
10.1007/s00125-007-0788-8
ISSN
0012-186X
Ausgabe der Veröffentlichung
10
Zeitschrift
Diabetologia
Schlüsselwörter
  • AMP-Activated Protein Kinases
  • Blood Glucose
  • Cloning, Molecular
  • DNA, Complementary
  • Genetic Variation
  • Genotype
  • Glucose
  • Glucose Tolerance Test
  • Humans
  • Insulin
  • Insulin Secretion
  • Lipids
  • Lipoproteins
  • Liver
  • Multienzyme Complexes
  • Protein Serine-Threonine Kinases
  • Protein Subunits
  • Reverse Transcriptase Polymerase Chain Reaction
  • White People
Sprache
eng
Country
Germany
Paginierung
2097 - 2106
Datum der Veröffentlichung
2007
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2008
Titel
Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
50

Datenquelle: PubMed

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