Wild Alaskan Vaccinium berries, V. vitis-idaea (lowbush cranberry) and V. uliginosum (bog blueberry), were investigated in parallel to their commercial berry counterparts; V. macrocarpon (cranberry) and V. angustifolium (lowbush blueberry). Lowbush cranberry accumulated about twice the total phenolics (624.4 mg/100 g FW) and proanthocyanidins (278.8 mg/100 g) content as commercial cranberries, but A-type proanthocyanidins were more prevalent in the latter. Bog blueberry anthocyanin and total phenolic contents of 220 and 504.5 mg/100 g, respectively, significantly exceeded those of the lowbush blueberry. Chlorogenic acid, however, was quite high in lowbush blueberry (83.1 mg/100 g), but undetected in bog blueberry, and the proanthocyanidins of lowbush blueberry had significantly higher levels of polymerization. Antioxidant capacity (DPPH, APTS and FRAP) correlated with phenolic content for each berry. A polyphenol-rich fraction from lowbush cranberry exhibited dose-dependent inhibition of LPS-elicited induction of IL-1β in RAW 264.7 cells, indicative of strong anti-inflammatory activity. These results corroborate the historic use of wild Alaskan berries as medicinally-important foods in Alaska Native communities.

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This study was designed to investigate the effects of physical conditioning on the expression of the insulin sensitive glucose transporter 4 protein (GLUT4) on mononuclear cells and HOMA-IR levels in dogs and compared to results reported in human skeletal muscle and the skeletal muscle of rodent models. Blood was sampled from conditioned dogs (n=8) and sedentary dogs (n=8). The conditioned dogs were exercised four months prior the experiment and were following a uniform training protocol, whereas the sedentary dogs were not. GLUT4 expression in mononuclear cells and plasma insulin levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA). Blood glucose levels were determined using blood plasma. HOMA-IR was calculated using plasma insulin and blood glucose levels using the linear approximation formula. Our results indicate that the state of conditioning had a significant effect on the GLUT4 expression at the surface of mononuclear cells. HOMA-IR was also affected by conditioning in dogs. GLUT4 levels in mononuclear cells of sled dogs were inversely correlated with the homeostasis model assessment of insulin sensitivity. This study demonstrates that conditioning increases GLUT4 levels in mononuclear cells of sled dogs as it has been previously reported in skeletal muscle. Our results support the potential of white blood cells as a proxy tissue for studying insulin signaling and may lead to development of a minimally invasive and direct marker of insulin resistance. This may be the first report of GLUT4 in mononuclear cells in response to exercise and measured with ELISA.

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Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS.

Using sled dogs as exercise model, our objectives of this study were to (1) assess the effects of one acute bout of high-intensity exercise on surface GLUT4 concentrations on easily accessible peripheral blood mononuclear cells (PBMC) and (2) compare our findings with published research on exercise induced GLUT4 in skeletal muscle. During the exercise bout, dogs ran 5 miles at approximately 90% of VO2 max. PMBC were collected before exercise (baseline), immediately after exercise and after 24 h recovery.GLUT4 was measured via ELISA. Acute exercise resulted in a significant increase on surface GLUT4 content on PBMC. GLUT4 was increased significantly immediately after exercise (~50%; p<0.05) and reduced slightly by 24 h post-exercise as compared to baseline (~22%; p>0.05). An effect of acute exercise on GLUT4 levels translocated to the cell membrane was observed, with GLUT4 levels not yet returned to baseline after 24 h post-exercise. In conclusion, the present investigation demonstrated that acute high-intensity exercise increased GLUT4 content at the surface of PBMC of sled dogs as it has been reported in skeletal muscle in other species. Our findings underline the potential use of peripheral blood mononuclear cell GLUT4 protein content as minimally invasive proxy to investigate relationships between insulin sensitivity, insulin resistance, GLUT4 expression and glucose metabolism.

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