Abstract
Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate insulin secretion and T cell differentiation, respectively. Moreover, various PPAR agonists prevent diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. PPARs are thus of interest in type 1 diabetes (T1D) as they represent a novel approach targeting both the pancreas and the immune system. In this review, we examine the role of PPARs in immune responses and beta cell biology and their potential as targets for treatment of T1D.
Highlights
type 1 diabetes (T1D) is an autoimmune disease caused by the pancreatic beta cells being dysfunctional or killed by autoreactive T cells resulting in reduced insulin production and hyperglycemia [1, 2]
The effects of Peroxisome proliferator-activated receptors (PPARs) activation on T cell survival, activation, and differentiation are likely beneficial in a T1D setting but remain unstudied to a large extent
The same is true for studies of pancreas biology with most studies being conducted in relation to type 2 diabetes
Summary
T1D is an autoimmune disease caused by the pancreatic beta cells being dysfunctional or killed by autoreactive T cells resulting in reduced insulin production and hyperglycemia [1, 2]. PPARs are involved in a mechanism termed “transrepression,” which is a ligand-dependent but PPRE-independent mechanism of gene repressions through interactions with other proteins such as NFκB, AP1, and STAT [25,26,27]. PPARγ is expressed in various tissues including adipose, intestine, liver, and kidney [30, 31] It is involved in regulating fat cell differentiation, lipid storage, and differentiation of monocytes into macrophages [32, 33]. An interesting feature is that women seem to be more susceptible than men to develop autoimmune diseases [42] This might be connected to PPAR expression as mouse studies have found that male mice have higher expression of PPARα in T cells compared to female mice, and that expression was androgen sensitive [43]. PPARγ is associated with the development of insulin resistance and type 2 diabetes [45]
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