Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis.

Skeletal muscle accounts for ~80% of insulin-stimulated glucose uptake. The Group I p21-activated kinase 1 (PAK1) is required for the non-canonical insulin-stimulated GLUT4 vesicle translocation in skeletal muscle cells. We found that the abundances of PAK1 protein and its downstream effector in muscle, ARPC1B, are significantly reduced in the skeletal muscle of humans with type 2 diabetes, compared to the non-diabetic controls, making skeletal muscle PAK1 a candidate regulator of glucose homeostasis.

Evidence for functional G-coupled protein receptors 43 and 120 in subcutaneous and intramuscular adipose tissue of Angus crossbred steers.

We conducted 3 independent experiments to demonstrate functional G-coupled protein receptor 43 (GPR43) and GPR120 in bovine intramuscular (i.m.) and subcutaneous (s.

SOX9+/PTF1A+ Cells Define the Tip Progenitor Cells of the Human Fetal Pancreas of the Second Trimester.

Significant progress has been made in recent years in characterizing human multipotent progenitor cells (hMPCs) of the early pancreas; however, the identity and persistence of these cells during the second trimester, after the initiation of branching morphogenesis, remain elusive. Additionally, studies on hMPCs have been hindered by few isolation methods that allow for the recovery of live cells. Here, we investigated the tip progenitor domain in the branched epithelium of human fetal pancreas between 13.

Syntaxin 4 Expression in Pancreatic β-Cells Promotes Islet Function and Protects Functional β-Cell Mass.

Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves the success of transplants in reversing streptozotocin (STZ)-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward a further understanding of this, human islets and inducible transgenic mice that selectively overexpress Stx4 in islet β-cells (βTG-Stx4) were challenged with proinflammatory stressors in vitro and in vivo. Remarkably, βTG-Stx4 mice resisted the loss of β-cell mass and the glucose intolerance that multiple low doses of STZ induce.

Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks: PAK-Ing Them Out.

Glucose is the principal cellular energy source in humans and maintenance of glucose homeostasis is critical for survival. Glucose uptake into peripheral skeletal muscle and adipose tissues requires the trafficking of vesicles containing glucose transporter-4 (GLUT4) from the intracellular storage compartments to the cell surface. Trafficking of GLUT4 storage vesicles is initiated the canonical insulin signaling cascade in skeletal muscle and fat cells, as well as exercise-induced contraction in muscle cells.