[Polymorphism of pro12Ala in peroxisome proliferator activated receptor gamma 2 (PPAgamma2): beta cell function and insulin sensitivity].
OBJECTIVE
The peroxisome proliferator-activated receptor isoform gamma (PPAR gamma) is a key regulator in lipid and glucose homoeostasis. A common polymorphism (Pro12Ala in PPAR gamma 2, prevalence ca. 25%) was shown to be associated with a decreased risk of type 2 diabetes. Generally, both beta-cell dysfunction and insulin resistance contribute to the development of type 2 diabetes. Therefore, the aim of the present study was to assess the mechanism by which the Ala allele of this polymorphism contributes to the reduced risk for type 2 diabetes.


METHODS
We studied 51 subjects without (Pro/Pro) and 26 subjects with this polymorphisms (X/Ala) (both groups non-diabetic) by a modified hyperglycaemic clamp which permitted determination of both insulin secretion (in response to glucose, GLP-1 and arginine) and insulin sensitivity.


RESULTS
None of the various phases of insulin secretion was significantly different between the 2 genotype groups (all p values > 0.13). In contrast, insulin sensitivity was significantly greater in X/Ala (0.19 +/- 0.03 U) compared to Pro/Pro (0.14 +/- 0.01 U, p = 0.04). In a two-dimensional assessment of insulin sensitivity and secretion, the homozygous alanine carriers appeared to have the most favourable constellation.


CONCLUSIONS
These simultaneously obtained data for insulin secretion and sensitivity strongly suggest that the mechanism by which the Ala allele contributes to a risk reduction for type 2 diabetes most likely involves an increase in insulin sensitivity.
Fritsche
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Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany.
Madaus
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A
Tschritter
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Ozeker
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M
Wulle
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EL
Machicao
F
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Häring
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H
Stumvoll
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D000328:Adult; D000409:Alanine / Q000235:genetics*; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000409:Alanine