PPAR-γ Agonists and Their Role in Type 2 Diabetes Mellitus Management

Abstract

Type 2 diabetes mellitus and obesity are the most frequent endocrine-metabolic diseases in the world and their pathogenic basis are characterized by insulin resistance and insulin secretion defects that can be demonstrated through several alterations in carbohydrates, lipids, and protein metabolism. The peroxisome proliferator-activated receptors have been identified as key regulators of glucose and lipid metabolism, because they act as transcription factors that stimulate protein synthesis in a wide variety of processes (energetic metabolism, proliferation, and cellular differentiation), of which have been identified 3 types (alpha, beta/delta, gamma). The thiazolidenediones are compounds that act as agonists of the peroxisome proliferator-activated receptor-gamma increasing the tissues sensibility (muscle, adiposity tissue, and liver) to the insulin action; that is why they are used nowadays in treatment of type 2 diabetes mellitus. These drugs produce several of adverse effects, such as weight increased, edema, anemia, pulmonary edema, and congestive cardiac failure. Even their use have been related for some studies to an increased in the myocardium infarct risk; this correlation has not been a strong determinant to remove them from the market.

Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis

“…These genes are highly significant for adipocyte differentiation and regulation of lipid metabolism. Notably, polymorphisms in PPARγ and Lpin1 genes are associated with metabolic syndromes and type 2 diabetes (T2D), and PPAR γ activation by insulin-sensitizing drugs can be used in T2D treatment [27,28]. …”

Assessment of the pharmacokinetics of co-administered metformin and lobeglitazone, a thiazolidinedione antihyperglycemic agent, in healthy subjects

“…Thiazolidinediones are selective ligands for peroxisome proliferator-activated receptor (PPAR)-g, a key regulator of glucose and lipid metabolism 5 . Thiazolidinediones lower blood glucose levels through several mechanisms including stimulation of gene expression for increasing fat oxidation and adiponectin release, as well as stimulation of adipocyte differentiation 6,7 .…”

Anti-diabetic properties ofDaphniphyllum macropodumfruit and its active compound

“…PPAR isoforms (α, β/δ, and γ) have been identified as key regulators of glucose absorption, lipid metabolism, proliferation, and cellular differentiation. 3,4) Recent clinical trials of the peroxisome proliferator-activated receptor γ (PPARγ) agonist thiazolidinedione have shown a significant improvement of tissue (muscle, adipose tissue, and liver) sensitivity to the effects of insulin, which is used in the treatment of T2DM. 3) There are numerous animal models for the study of T2DM and the ideal pathological models are considered as the developing process and metabolic characteristics of human T2DM.…”

“…3,4) Recent clinical trials of the peroxisome proliferator-activated receptor γ (PPARγ) agonist thiazolidinedione have shown a significant improvement of tissue (muscle, adipose tissue, and liver) sensitivity to the effects of insulin, which is used in the treatment of T2DM. 3) There are numerous animal models for the study of T2DM and the ideal pathological models are considered as the developing process and metabolic characteristics of human T2DM. 5) Although genetic obese diabetic animals are commonly used, T2DM is a complex polygenic disease and interaction with environment influences, such as high-caloric fat diets.…”