The observation that thiazolidinediones enhance skeletal muscle insulin sensitivity in obesity and in patients with non-insulin-dependent diabetes mellitus (NIDDM), by activating PPARgamma, and possibly by inducing its expression, suggests that PPARgamma expression in skeletal muscle plays a key role in determining tissue sensitivity to insulin, and that PPARgamma expression may be decreased in insulin resistant subjects.
Increased expression of PPARgamma protein and other genes involved in glucose and lipid metabolism in skeletal muscle may account, in part, for the insulin sensitizing effects of troglitazone in type II diabetes.
Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.
Overexpression of PPARalpha and PPARbeta mRNA and inhibition of PPARgamma mRNA expression were also observed in monocyte-derived macrophages isolated from patients with type 2 diabetes.
These results suggest that the PPARgamma is a thrifty gene and that the Pro12Ala PPARgamma2 polymorphism protects against type 2 diabetes in the Japanese.
When taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least two genes are involved in determining susceptibility to the disease in these people.
The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates fat-cell development and glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the management of type 2 diabetes mellitus.
We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(PPARgamma) with type 2 diabetes.
Based on our preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPARgamma ligand used for the treatment of type 2 diabetes.
The association of the Pro12Ala and Pro115GlnPPARgamma2 gene variants with type 2 diabetes mellitus, the body mass index (BMI), and other diabetes-related phenotypes was examined in the Taiwanese population.
This issue is important because thiazolidinediones, which are ligands for PPARgamma, have recently been approved for the treatment of type 2 diabetes, a state of accelerated atherosclerosis.
Since this amino acid substitution may cause a reduction in the transcriptional activity of PPARgamma, this polymorphism may be associated with decreased insulin resistance and decreased risk of type 2 diabetes.
The associations found between polymorphisms in the PPAR gamma gene and type 2 diabetes suggest that either the A12 isofrom is functional leading to a predisposition to type 2 diabetes in homozygotes or that there is a third, unknown mutation linked to the A12/c1431 haplotype which is responsible.
Since this amino acid substitution may cause a reduction in the transcriptional activity of PPARgamma, this polymorphism may be associated with decreased insulin resistance and decreased risk of Type 2 diabetes.
We investigated whether known variants in the PPARgamma-2 gene are associated with the occurrence of coronary heart disease (CHD) in 365 patients with type 2 diabetes, prospectively characterised for the presence or absence of CHD.
The polymorphisms of two genes have recently been associated with complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome proliferator-activated receptor-gamma (PPARgamma).
To elucidate the mechanism of interaction between genetic and environmental factors in development of type 2 diabetes, we analyzed prevalence and metabolic status in the context of the variant form of PPARgamma in 105 native Japanese and 145 Japanese American, both should have different environmental factors.
The peroxisome proliferator-activated receptor gamma (PPARgamma) and calpain-10 (CAPN10) genes have recently been identified as T2DM susceptibility genes, and the lessons learnt from these studies are helping to shape future strategies to search for additional susceptibility genes in T2DM and insulin resistance.
Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus.
Although thiazolidinediones represent a major therapy for type 2 diabetes, conflicting studies showing that these agents can increase or decrease colonic tumors in mice have raised concerns about the role of PPARgamma in colon cancer.
The influence of the Pro12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-naïve patients with type 2 diabetes.
Our results add to the concern that the clinical use of insulin-sensitizing PPARgamma agonists (i.e. thiazolidinediones) to treat Type 2 Diabetes could exacerbate atherosclerosis, and highlight the need for clinical trials that address this issue.