Amino acid homeostasis is a target of metformin therapy.

Objective: Unexplained changes in regulation of branched chain amino acids (BCAA) during diabetes therapy with metformin have been known for years. Here we have investigated mechanisms underlying this effect.

Methods: We used cellular approaches, including single gene/protein measurements, as well as systems-level proteomics.

Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status.

Rationale: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood.

Objective: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties.

Methods And Results: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α-dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2).

Insulin sensitization therapy and the heart: focus on metformin and thiazolidinediones.

Chronic heart failure (CHF) is an insulin-resistant (IR) state and the degree of IR is related to disease severity and poor clinical outcome in CHF. IR may be pathophysiologically linked with CHF. Therefore, IR may represent a new target for treatment in CHF.

The effect of metformin on insulin resistance and exercise parameters in patients with heart failure.

Aims: Chronic heart failure (CHF) is an insulin-resistant state. The degree of insulin resistance (IR) correlates with disease severity and is associated with reduced exercise capacity. In this proof of concept study, we have examined the effect of metformin on IR and exercise capacity in non-diabetic CHF patients identified to have IR.

Effect of Metformin on mortality in patients with heart failure and type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) plus chronic heart failure (CHF) is a common but lethal combination and therapeutic options are limited. Metformin is perceived as being relatively contraindicated in this context, although mounting evidence indicates that it may be beneficial. This study was carried out to investigate the use of metformin therapy for treating patients with DM and CHF in a large population-based cohort study.

AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease.

AMPK (AMP-activated protein kinase) is a heterotrimetric enzyme that is expressed in many tissues, including the heart and vasculature, and plays a central role in the regulation of energy homoeostasis. It is activated in response to stresses that lead to an increase in the cellular AMP/ATP ratio caused either by inhibition of ATP production (i.e.

Insulin resistance: a potential new target for therapy in patients with heart failure.

There is increasing evidence to suggest that chronic heart failure (CHF) is an insulin resistant (IR) state and that the degree of IR correlates with the severity and mortality of CHF. The pathophysiology of IR in CHF has yet to be fully defined. Additionally, it remains to be determined if IR is merely a marker reflecting the severity of CHF or whether it contributes to the disease in CHF.