SciCombinator

 To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).

 To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.

Recent in vitro and animal experiments suggest that peroxisome proliferation-activated receptor gamma (PPARɣ) agonist medications, such as antidiabetic glitazone (GTZ) drugs, are neuroprotective in models of Parkinson’s disease (PD). These findings have not been tested in humans. We hypothesized that individuals prescribed GTZ drugs would have a lower incidence of PD compared to individuals prescribed other treatments for diabetes.

 To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones).

The management of type 2 diabetes has been challenged by uncertainty about possible cardiovascular effects related to treatment intensity and choice of drug. Although the Food and Drug Administration (FDA) considers a decrease in glycated hemoglobin an approvable end point, very intensive glycemic control is associated with increased cardiovascular and all-cause mortality.(1) The safety of specific drugs for type 2 diabetes - particularly the thiazolidinediones - has also been questioned. After rosiglitazone had been approved in the United States in 1999 and in Europe in 2000, a highly publicized meta-analysis in 2007 reported a 43% increase in myocardial infarction (P=0.03) . . .

Thiazolidine-2,4-dione is an extensively explored heterocyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications, cancer, arthritis, inflammation, microbial infection, and melanoma, etc. The current paradigm of drug development has shifted to the structure-based drug design, since high-throughput screenings have continued to generate disappointing results. The gap between hit generation and drug establishment can be narrowed down by investigation of ligand interactions with its receptor protein. Therefore, it would always be highly beneficial to gain knowledge of molecular level interactions between specific protein target and developed ligands; since this information can be maneuvered to design new molecules with improved protein fitting. Thus, considering this aspect, we have corroborated the information about molecular (target) level implementations of thiazolidine-2,4-diones (TZD) derivatives having therapeutic implementations such as, but not limited to, anti-diabetic (glitazones), anti-cancer, anti-arthritic, anti-inflammatory, anti-oxidant and anti-microbial, etc. The structure based SAR of TZD derivatives for various protein targets would serve as a benchmark for the alteration of existing ligands to design new ones with better binding interactions.

The aim of this study was to compare the effect of the resveratrol with gliclazide and losartan in streptozotocin induced diabetic rats.

This study aimed to develop a new stable nanoformulation of silymarin (SM) with optimum enhanced oral bioavailability and to evaluate its effect as well as mechanism of action as a superior antidiabetic agent over native SM using streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents.

Loss-of-function mutations inPPARGcause familial partial lipodystrophy type 3 (FPLD3) and severe metabolic disease in many cases. Missense mutations inPPARGare present in ∼1:500 people. Whilst mutations are often binarily classified as ‘benign’ or ‘deleterious’, prospective functional classification of all missensePPARGvariants suggests that their impact is graded. Furthermore, in testing novel mutations with both prototypic ‘endogenous’ (e.g. prostaglandin J2 (PGJ2)) and synthetic ligands (thiazolidinediones, tyrosine agonists), we observed that synthetic agonists selectively rescue function of some PPARγ mutants. Here, we report FPLD3 patients, harbouring two such PPARγ mutations (R308P, A261E). Both PPARγ mutants exhibit negligible constitutive or PGJ2-induced transcriptional activity but respond readily to synthetic agonistsin vitro, with structural modelling providing a basis for such differential ligand-dependent responsiveness. Concordant with this, dramatic clinical improvement was seen following pioglitazone treatment of the patient with R308P mutant PPARγ. A patient with A261E mutant PPARγ also responded beneficially to rosiglitazone, though cardiomyopathy precluded prolonged thiazolidinedione use. These observations indicate that detailed structural and functional classification can be used to inform therapeutic decisions in patients withPPARGmutations.