How does PPAR gamma increase insulin sensitivity?
How does PPAR gamma increase insulin sensitivity?
PPAR-γ agonists decrease circulating triglyceride and free fatty acid levels by repartitioning fatty acids in adipocytes. Increased free fatty acids are associated with hepatic insulin resistance, resulting in the increased gluconeogenesis (47).
What does PPAR gamma do?
PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells. PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.
What is PPAR diabetes?
Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk.
How does PPAR gamma agonist be used as antidiabetic drug?
These compounds improve insulin resistance by increasing cell sensitivity to insulin. In fact, PPAR gamma agonists increase peripheral insulin sensitivity by increasing the transcription of genes, which, in turn, increase glucose uptake, also improving insulin-stimulated glucose disposal in muscle.
Is there a genetic link between diabetes and PPAR-γ?
Patients with a dominant-negative mutation in the PPAR-γ gene show severe hyperglycemia, which provides a genetic link between PPAR-γ and type 2 diabetes ( 7 ).
How does PPAR-γ affect pancreatic β cells?
In addition, PPAR-γ can directly affect liver and pancreatic β-cells to improve glucose homeostasis. Type 2 diabetes affects >5% of the population. The major underlying defect of type 2 diabetes is insulin resistance and progressive deterioration of β-cell functions ( 1 ).
What is the effect of PPAR-γ2 on adipose tissue?
The effect on the individual is weak, but because of a prevalence of >75% of the high-risk Pro allele, the population-attributable risk is enormous. The in vivo effects of the polymorphism are secondary to alterations in adipose tissue, where PPAR-γ2 is predominantly expressed.
How does PPAR-γ contribute to glucose homeostasis?
Improved glucose homeostasis may be achieved either by systemic insulin sensitization or by direct action of PPAR-γ on the transcription of genes involved in the glucose disposal. Evidence supporting the direct action of PPAR-γ on glucose metabolism has been reported.
