An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases.

Peroxisome proliferator-activated receptors (PPARs) are a superfamily of nuclear transcription receptors, consisting of PPARα, PPARγ, and PPARβ/δ, which are highly expressed in the liver. They control and modulate the expression of a large number of genes involved in metabolism and energy homeostasis, oxidative stress, inflammation, and even apoptosis in the liver. Therefore, they have critical roles in the pathophysiology of hepatic diseases.

Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4.

Objective: This study was conducted to define a safe, effective dose regimen for metformin in moderate and severe chronic kidney disease (CKD; stages 3A/3B and 4, respectively), after the lifting of restrictions on metformin use in patients with diabetes with moderate-to-severe CKD in the absence of prospective safety and efficacy studies.

Research Design And Methods: Three complementary studies were performed: ) a dose-finding study in CKD stages 1-5, in which blood metformin concentrations were evaluated during a 1-week period after each dose increase; ) a 4-month metformin treatment study for validating the optimal metformin dose as a function of the CKD stage (3A, 3B, and 4), with blood metformin, lactate, and HbA concentrations monitored monthly; and ) an assessment of pharmacokinetic parameters after the administration of a single dose of metformin in steady-state CKD stages 3A, 3B, and 4.

Results: First, in the dose-finding study, the appropriate daily dosing schedules were 1,500 mg (0.

Renoprotective Effects of Metformin.

Background/aims: It has become clear that metformin exerts pleiotropic actions beyond its glucose-lowering agent effect. In this review, we summarise the state of the art concerning the potential renoprotective effects of metformin in vitro, animal models and clinical nephrology.

Methods: A literature search was performed in PUBMED, ScienceDirect, between January 1957 and March 2017 using the following keywords: "metformin," "nephroprotection," "renoprotection," "survival," "renal failure," "chronic kidney diseases," "fibrosis," "polycystic kidney disease" and "microalbuminuria.

Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm.

Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin-treated patients.