PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes.

The transcriptional coactivators peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1α or PGC-1β overexpression in C2C12 myotubes increased protein synthesis and myotube diameter under basal conditions and attenuated the loss in protein synthesis following the treatment with the catabolic agent, dexamethasone. To investigate whether PGC-1α or PGC-1β signal through the Akt/mTOR pathway to increase protein synthesis, treatment with the PI3K and mTOR inhibitors, LY294002 and rapamycin, respectively, was undertaken but found unable to block PGC-1α or PGC-1β's promotion of protein synthesis.

Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products.

Diarrhea is a common illness among travelers to resource-limited countries, the most prevalent attributable agent being enterotoxigenic (ETEC). At this time, there are no vaccines licensed specifically for the prevention of ETEC-induced traveler's diarrhea (TD), and this has propelled investigation of alternative preventive methods. Colostrum, the first milk expressed after birthing, is rich in immunoglobulins and innate immune components for protection of newborns against infectious agents.

Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin action.

The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting greater complexity describes mitochondrial regulation of insulin action.

3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes.

Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo.

We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these compounds were investigated in diabetic db/db mice, insulin-resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose and HbA(1c) levels in db/db mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering effects of exogenous insulin administration in rats with STZ-induced diabetes.

Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells.

Previous studies have shown that Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) exhibit triacylglycerol (TAG) lowering effect in vitro and in vivo by down-regulating the Sterol Regulating Element Binding Protein (SREBP-1c) and reducing the expression levels of lipogenic genes. However, there is no evidence on the effect of Docosapentaenoic Acid (DPA) on SREBP-1c expression levels. DPA is a long chain n-3 fatty acid present in our diet through fish, red meat and milk of ruminant animals.

Chemerin, a novel adipokine in the regulation of angiogenesis.

Context: Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in the adipose depots of obese compared with lean animals and was markedly elevated during differentiation of fibroblasts into mature adipocytes.

Objective: The objective of the study was to identify factors that affect the regulation and potential function of chemerin using a genetics approach.

The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome.

The human Abelson helper integration site-1 (AHI1) gene is associated with both neurologic and hematologic disorders; however, it is also located in a chromosomal region linked to metabolic syndrome phenotypes and was identified as a type 2 diabetes mellitus susceptibility gene from a genomewide association study. To further define a possible role in type 2 diabetes mellitus development, AHI1 messenger RNA expression levels were investigated in a range of tissues and found to be highly expressed in skeletal muscle as well as displaying elevated levels in brain regions and gonad tissues. Further analysis in a rodent polygenic animal model of obesity and type 2 diabetes mellitus identified increased Ahi-1 messenger RNA levels in red gastrocnemius muscle from fasted impaired glucose-tolerant and diabetic rodents compared with healthy animals (P < .

The measurement of GLUT4 translocation in 3T3-L1 adipocytes.

Type 2 diabetes (T2D) is one of the fastest growing threats to human health in westernised and developing countries and is associated with central obesity, atherosclerosis, dyslipidaemia, hyperinsulinaemia and hypertension. Insulin resistance, defined as a diminished response to ordinary levels of circulating insulin in one or more peripheral tissues, is an integral feature of T2D pathophysiology. This includes an impairment of insulin to inhibit hepatic glucose output and to stimulate glucose disposal into muscle and fat.

Increased insulin-stimulated Akt pSer473 and cytosolic SHP2 protein abundance in human skeletal muscle following acute exercise and short-term training.

The purpose of the present study was to determine in human skeletal muscle whether a single exercise bout and 7 days of consecutive endurance (cycling) training 1) increased insulin-stimulated Akt pSer(473) and 2) altered the abundance of the protein tyrosine phosphatases (PTPases), PTP1B and SHP2. In healthy, untrained men (n = 8; 24 +/- 1 yr), glucose infusion rate during a hyperinsulinemic euglycemic clamp, when compared with untrained values, was not improved 24 h following a single 60-min bout of endurance cycling but was significantly increased ( approximately 30%; P < 0.05) 24 h following completion of 7 days of exercise training.

A purine analog kinase inhibitor, calcium/calmodulin-dependent protein kinase II inhibitor 59, reveals a role for calcium/calmodulin-dependent protein kinase II in insulin-stimulated glucose transport.

Olomoucine is known as a cyclin-dependent kinase inhibitor. We found that olomoucine blocked insulin's ability to stimulate glucose transport. It did so without affecting the activity of known insulin signaling proteins.