scholarly journals Mutation analysis of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus

Diabetologia ◽  
2001 ◽  
Vol 44 (12) ◽  
pp. 2220-2226 ◽  
Author(s):  
J. Ek ◽  
G. Andersen ◽  
S. A. Urhammer ◽  
P. H. Gæde ◽  
T. Drivsholm ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Amino Acid ◽  
Mutation Analysis ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Analysis of the Relationship between Type II Diabetes Mellitus and Parkinson’s Disease: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Fauze Camargo Maluf ◽  
David Feder ◽  
Alzira Alves de Siqueira Carvalho
Keyword(s):  
Diabetes Mellitus ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Alpha Synuclein ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Peroxisome Proliferator Activated Receptor

In the early sixties, a discussion started regarding the association between Parkinson’s disease (PD) and type II diabetes mellitus (T2DM). Today, this potential relationship is still a matter of debate. This review aims to analyze both diseases concerning causal relationships and treatments. A total of 104 articles were found, and studies on animal and “in vitro” models showed that T2DM causes neurological alterations that may be associated with PD, such as deregulation of the dopaminergic system, a decrease in the expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), an increase in the expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes 15 (PED/PEA-15), and neuroinflammation, as well as acceleration of the formation of alpha-synuclein amyloid fibrils. In addition, clinical studies described that Parkinson’s symptoms were notably worse after the onset of T2DM, and seven deregulated genes were identified in the DNA of T2DM and PD patients. Regarding treatment, the action of antidiabetic drugs, especially incretin mimetic agents, seems to confer certain degree of neuroprotection to PD patients. In conclusion, the available evidence on the interaction between T2DM and PD justifies more robust clinical trials exploring this interaction especially the clinical management of patients with both conditions.

scholarly journals Review of the Structural and Dynamic Mechanisms of PPARγPartial Agonism

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Alice J. Kroker ◽  
John B. Bruning
Keyword(s):  
Side Effects ◽  
Type Ii Diabetes ◽  
Acid Metabolism ◽  
Type Ii Diabetes Mellitus ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Agonists ◽  
Dynamic Mechanisms ◽  
Binding Cavity

PPARγ(peroxisome proliferator activated receptorγ) is a ligand activated transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. While endogenous ligands of PPARγinclude fatty acids and eicosanoids, synthetic full agonists of the receptor, including members of the thiazolidinedione (TZD) class, have been widely prescribed for the treatment of type II diabetes mellitus (T2DM). Unfortunately, the use of full agonists has been hampered by harsh side effects with some removed from the market in many countries. In contrast, partial agonists of PPARγhave been shown to retain favourable insulin sensitizing effects while exhibiting little to no side effects and thus represent a new potential class of therapeutics for the treatment of T2DM. Partial agonists have been found to not only display differences in transcriptional and cellular outcomes, but also act through distinct structural and dynamic mechanisms within the ligand binding cavity compared to full agonists.

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