[Polymorphism of pro12Ala in peroxisome proliferator activated receptor gamma 2 (PPAgamma2): beta cell function and insulin sensitivity]

Dtsch Med Wochenschr. 2001 May 18;126(20):580-4. doi: 10.1055/s-2001-14103.
[Article in German]


Background and 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.

Patients and 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.

Conclusion: 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.

Publication types

  • English Abstract

MeSH terms

  • Adult
  • Alanine / genetics*
  • Alleles*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Female
  • Gene Expression Regulation / physiology
  • Genotype
  • Glucose Tolerance Test
  • Heterozygote
  • Homozygote
  • Humans
  • Insulin Resistance / genetics*
  • Insulin Resistance / physiology
  • Islets of Langerhans / physiology*
  • Male
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Transcription Factors / genetics*


  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Alanine