Thiazolidinediones and Type 2 Diabetes: From Cellular Targets to Cardiovascular Benefit

Papaetis, Georgios S.; Orphanidou, Dora; Panagiotou, Themistoklis N.

doi:10.2174/138945011796818243

Cited by 18 publications

(20 citation statements)

References 167 publications

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“…Subcutaneous WAT is by far the largest adipose depot within the human body. Visceral WAT (mainly composed by omental, mesenteric, retroperitoneal and epicardial fat) constitutes about 15% of total fat in obese individuals [ 27 , 31 ].…”

Section: Adipokines and Other Molecules That May Induce Insulin Resismentioning

confidence: 99%

State of the art paper Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

Papaetis¹,

Papakyriakou²,

Panagiotou³

2015

aoms

116

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The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent β-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D.

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Section: Adipokines and Other Molecules That May Induce Insulin Resismentioning

confidence: 99%

State of the art paper Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

Papaetis¹,

Papakyriakou²,

Panagiotou³

2015

aoms

116

View full text Add to dashboard Cite

show abstract

“…They specifically target insulin resistance by enhancing certain actions of insulin on carbohydrates and lipids metabolism [1][2][3][4]. The most frequently used thiazolidinedione is pioglitazone.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone

Alzoubi

Khabour

Hussain

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…One is to find the means of enhancing the anabolic response to promote the safe storage of nutrients into inert macromolecules. For example, thiazolidinediones, which were once widely prescribed (13), promote adipocyte differentiation and induce enzymes that promote triglyceride synthesis and thus increase the capacity of the organism to safely store fat (14). A second approach has been to promote catabolism of the harmful metabolites.…”

mentioning

confidence: 99%

Ablation of Dihydroceramide Desaturase 1, a Therapeutic Target for the Treatment of Metabolic Diseases, Simultaneously Stimulates Anabolic and Catabolic Signaling

Siddique

Liu

Wang

et al. 2013

Molecular and Cellular Biology

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The lipotoxicity hypothesis posits that obesity predisposes individuals to metabolic diseases because the oversupply of lipids to tissues not suited for fat storage leads to the accumulation of fat-derived molecules that impair tissue function. Means of combating this have been to stimulate anabolic processes to promote lipid storage or to promote catabolic ones to drive fat degradation. Herein, we demonstrate that ablating dihydroceramide desaturase 1 (Des1), an enzyme that produces ceramides, leads to the simultaneous activation of both anabolic and catabolic signaling pathways. In cells lacking Des1, the most common sphingolipids were replaced with dihydro forms lacking the double bond inserted by Des1. These cells exhibited a remarkably strong activation of the antiapoptotic and anabolic signaling pathway regulated by Akt/protein kinase B (PKB), were resistant to apoptosis, and were considerably larger than their wild-type counterparts. Paradoxically, Des1؊/؊ cells exhibited high levels of autophagy. Mechanistic studies revealed that this resulted from impaired ATP synthesis due in part to decreased expression and activity of several complexes of the electron transport chain, particularly complex IV, leading to activation of AMP-activated protein kinase and its induction of the autophagosome. Thus, Des1 ablation enhanced starvation responses but dissociated them from the anabolic, prosurvival, and antiautophagic Akt/PKB pathways.

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Thiazolidinediones and Type 2 Diabetes: From Cellular Targets to Cardiovascular Benefit

Cited by 18 publications

References 167 publications

State of the art paper Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

State of the art paper Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone

Ablation of Dihydroceramide Desaturase 1, a Therapeutic Target for the Treatment of Metabolic Diseases, Simultaneously Stimulates Anabolic and Catabolic Signaling

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