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Thiazolidinediones address underlying causes of type 2 diabetes, although their mechanism of action is not clearly understood. The compounds are thought to function as direct activators of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor-gamma), although pioglitazone, the weaker agonist of the two thiazolidinediones now in clinical(More)
Facilitated pyruvate transport across the mitochondrial inner membrane is a critical step in carbohydrate, amino acid, and lipid metabolism. We report that clinically relevant concentrations of thiazolidinediones (TZDs), a widely used class of insulin sensitizers, acutely and specifically inhibit mitochondrial pyruvate carrier (MPC) activity in a variety of(More)
BACKGROUND Several techniques have been described for reconstruction of the medial patellofemoral ligament. However, the isometry of the medial patellofemoral ligament has not been studied. PURPOSE To define the anatomy and isometry of the medial patellofemoral ligament. STUDY TYPE Cadaveric study. METHODS The authors dissected the medial(More)
The oxazolidinones are one of the newest classes of antibiotics. They inhibit bacterial growth by interfering with protein synthesis. The mechanism of oxazolidinone action and the precise location of the drug binding site in the ribosome are unknown. We used a panel of photoreactive derivatives to identify the site of action of oxazolidinones in the(More)
Thiazolidinedione (TZD) insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of(More)
Currently approved thiazolidinediones (TZDs) are effective insulin-sensitizing drugs that may have efficacy for treatment of a variety of metabolic and inflammatory diseases, but their use is limited by side effects that are mediated through ectopic activation of the peroxisome proliferator-activated receptor γ (PPARγ). Emerging evidence suggests that the(More)
Oxazolidinone antibiotics, an important new class of synthetic antibacterials, inhibit protein synthesis by interfering with ribosomal function. The exact site and mechanism of oxazolidinone action has not been elucidated. Although genetic data pointed to the ribosomal peptidyltransferase as the primary site of drug action, some biochemical studies(More)
Four dopamine receptor agonists used for the treatment of Parkinson's disease (apomorphine, pergolide, ropinirole and sumanirole) were evaluated for the ability to block human ether-a-go-go related gene (hERG) K(+) channels and to modify the duration of canine Purkinje fiber action potentials. Apomorphine, pergolide and ropinirole blocked the hERG-mediated(More)
Insulin sensitizing thiazolidinediones (TZDs) are generally considered to work as agonists for the nuclear receptor peroxisome proliferative activated receptor-gamma (PPAR gamma). However, TZDs also have acute, non-genomic metabolic effects and it is unclear which actions are responsible for the beneficial pharmacology of these compounds. We have taken(More)
Major bottlenecks in the expansion of human β-cell mass are limited proliferation, loss of β-cell phenotype, and increased apoptosis. In our previous studies, activation of Wnt and mTOR signaling significantly enhanced human β-cell proliferation. However, isolated human islets displayed insulin signaling pathway resistance, due in part to chronic activation(More)