Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis.

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with type 1 or type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here, we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in an LDLR mouse model of atherosclerosis.

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice.

The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice.

Methionine restriction improves renal insulin signalling in aged kidneys.

Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.

Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice.

Aims: Methionine restriction (MR) and hepatic protein tyrosine phosphatase 1B (PTP1B) knockdown both improve hepatic insulin sensitivity by targeting different proteins within the insulin signaling pathway, as well as diminishing hepatic triglyceride content through decreasing hepatic lipogenesis. We hypothesized that a combined approach of hepatic PTP1B inhibition and methionine restriction could lead to a synergistic effect on improvements in glucose homeostasis and lipid metabolism.

Methods: Male and female hepatic PTP1B knockout (Alb-Ptp1b(-/-)) and control wild-type (Ptp1b(fl/fl)) mice were maintained on control diet (0.

Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals.

Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism.

Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B).

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.

Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance.