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Metabolite Profiling Reveals Normal Metabolic Control in Carriers of Mutations in the Glucokinase Gene (MODY2).

Spégel, Peter LU ; Ekholm, Ella LU ; Tuomi, Tiinamaija LU ; Groop, Leif LU ; Mulder, Hindrik LU and Filipsson, Karin LU (2012) In Diabetes
Abstract
Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite pattern similar to that of healthy individuals, while other forms of diabetes... (More)
Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite pattern similar to that of healthy individuals, while other forms of diabetes differed markedly in their metabolite profiles. Furthermore, despite elevated glucose concentrations, carriers of GCK mutations showed lower levels of free fatty acids and triglycerides than healthy control subjects. The metabolite profiling was confirmed by enzymatic assays and replicated in a cohort of 11 GCK-MODY patients. Elevated levels of fatty acids are known to associate with β-cell dysfunction, insulin resistance, and increased incidence of late complications. Our results show that GCK-MODY represents a metabolically normal condition, which may contribute to the lack of late complications and the nonprogressive nature of the disease. (Less)
Please use this url to cite or link to this publication:
author
organization
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type
Contribution to journal
publication status
published
subject
in
Diabetes
publisher
American Diabetes Association
external identifiers
  • WOS:000314263600037
  • PMID:23139355
  • Scopus:84873026980
ISSN
1939-327X
DOI
10.2337/db12-0827
language
English
LU publication?
yes
id
45417058-fb82-4e20-a821-59c0ed6572aa (old id 3219095)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23139355?dopt=Abstract
date added to LUP
2012-12-03 13:44:58
date last changed
2016-10-30 04:36:58
@misc{45417058-fb82-4e20-a821-59c0ed6572aa,
  abstract     = {Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite pattern similar to that of healthy individuals, while other forms of diabetes differed markedly in their metabolite profiles. Furthermore, despite elevated glucose concentrations, carriers of GCK mutations showed lower levels of free fatty acids and triglycerides than healthy control subjects. The metabolite profiling was confirmed by enzymatic assays and replicated in a cohort of 11 GCK-MODY patients. Elevated levels of fatty acids are known to associate with β-cell dysfunction, insulin resistance, and increased incidence of late complications. Our results show that GCK-MODY represents a metabolically normal condition, which may contribute to the lack of late complications and the nonprogressive nature of the disease.},
  author       = {Spégel, Peter and Ekholm, Ella and Tuomi, Tiinamaija and Groop, Leif and Mulder, Hindrik and Filipsson, Karin},
  issn         = {1939-327X},
  language     = {eng},
  month        = {11},
  publisher    = {ARRAY(0xb092fb0)},
  series       = {Diabetes},
  title        = {Metabolite Profiling Reveals Normal Metabolic Control in Carriers of Mutations in the Glucokinase Gene (MODY2).},
  url          = {http://dx.doi.org/10.2337/db12-0827},
  year         = {2012},
}