Temporal Baseline of Essesntial and Non-essential Elements Recorded in Baleen of Western Arctic Bowhead Whale (Balaena mysticetus).

This study established the first baseline of changing elemental concentrations in bowhead whale baleen over time (1958-1999). From previously published stable isotope data, year, season (summer or winter), and location (Beaufort or Bering/Chukchi seas) were attributed to each sample. Thirteen elements (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, V, Zn) in baleen from nine subsistence-harvested bowhead whales (n = 138) were detected. Al, Cu, and Fe were the highest concentrations while Cd and V were among the lowest. Our data supports absorption as the main route of exposure to environmental elements rather than biomagnification due to bowhead whales' low trophic position. A linear mixed-effects model confirmed most elements' concentrations increased with time, while location and sex were insignificant explanatory factors. These temporal fluctuations were most likely a product of environmental changes due to a warming climate and human activities.

Role of Receptors in Relation to Plaques and Tangles in Alzheimer's Disease Pathology.

Despite the identification of Aß plaques and NFTs as biomarkers for Alzheimer's disease (AD) pathology, therapeutic interventions remain elusive, with neither an absolute prophylactic nor a curative medication available to impede the progression of AD presently available. Current approaches focus on symptomatic treatments to maintain AD patients' mental stability and behavioral symptoms by decreasing neuronal degeneration; however, the complexity of AD pathology requires a wide range of therapeutic approaches for both preventive and curative treatments. In this regard, this review summarizes the role of receptors as a potential target for treating AD and focuses on the path of major receptors which are responsible for AD progression. This review gives an overall idea centering on major receptors, their agonist and antagonist and future prospects of viral mimicry in AD pathology. This article aims to provide researchers and developers a comprehensive idea about the different receptors involved in AD pathogenesis that may lead to finding a new therapeutic strategy to treat AD.

Effects of Methylmercury and Theaflavin Digallate on Adipokines in Mature 3T3-L1 Adipocytes.

Diabetes is a contributor to morbidity across the globe and is often associated with obesity, metabolic syndrome and other inflammatory diseases associated with aging. In addition to genetic and lifestyle factors, environmental factors such as metals and persistent organic pollutants may increase the severity or lower the threshold of these conditions. In cell culture, methylmercury is toxic to adipocytes and may impact adipokine secretions. In this study, we determined the effects of different concentrations of theaflavin digallate on methylmercury exposed 3T3-L1 adipocytes in cell culture. Secretions of resistin, adiponectin and lipid peroxidation product, 4-hydroxynonenal (4-HNE) were monitored using ELISA assays. Cell morphology of methylmercury and theaflavin-3,3'-digallate treated adipocytes was assessed using Lipid (Oil Red O) staining. Exposure to methylmercury increased the levels of resistin and adiponectin as well as 4-HNE when compared to the control cells. Methylmercury treated cells resulted in smaller number of adipocytes and clumped lipid droplets. These results suggest that methylmercury induces reactive oxygen species leading to development of an inflammatory response. Theaflavin-3,3'-digallate reduced the impact of methylmercury by maintaining the adipocytes morphology and secretion patterns of adiponectin, resistin and 4-hydroxynonenal. With this experimental model system other anti-inflammatory and signaling agents could be tested at the biochemical level before eventually leading to studies in animal models.

Managing environmental risks: the benefits of a place-based approach.

CONTEXT: Effective management of environmental risks such as food and water contamination requires both high quality scientific information and effective, informed social policy. Not only must health practitioners and policy-makers recognize the complexities of human health as a social phenomenon, they must also negotiate the vagaries of uncertainty, precaution, and ethics in their implementation of public health guidelines and advisories. For example, some health practitioners in Alaska have argued against implementation of US Environmental Protection Agency and World Health Organization's standardized consumption advisories for methylmercury (MeHg) in fish, in favor of place-based approaches to evaluating and communicating risk. They stress the importance of traditional subsistence foods and lifestyles, along with other local environmental, economic, and cultural drivers and determinants of environmental health. Such place-based approaches have been successful in improving health outcomes in Alaska and elsewhere. ISSUE: Nevertheless, debate continues regarding the validity and ethics of place-based approaches to developing and communicating standards and advice for managing environmental risks. Recent critiques suggest that place-based approaches to environmental health represent an undesirable kind of regional 'exceptionalism': the implication of which is that precaution, in respect to acting on the best available objective science, is undermined by attention to subjective local values. In this article we comment on this debate, a debate rooted in concerns regarding the delineation between science-based and policy-based decision-making. LESSONS LEARNED: Our experience with the social and ecological dimensions of MeHg contamination of fish and game in Alaska and elsewhere offers three considerations regarding the potential benefits available through place-based approaches: (1) they can contribute to the accuracy and systematic characterization of risks and their relationship to multiple direct and indirect health outcomes; (2) they are more likely to inform actual changes in behavior; and (3) they afford greater transparency to the risk management process and therefore facilitate environmental justice. We stress that standardized risk assessments and advisories remain important for providing a precautionary baseline that can inform the management and enforcement of industrial and other polluting activities at the state level. However, the management of environmental health at the regional and local level requires an approach that is cognizant of local circumstances and needs, and addresses health in a systemic and integrative fashion capable of incorporating qualitative social, cultural, and economic drivers and determinants. Thus, we recommend a two-tiered approach that blends state-based and place-based environmental risk management.

Engaging Students in Science Courses: Lessons of Change from the Arctic.

Where you live should have something to do with what you teach. In the Arctic, this idea of place-based education-teaching and sharing knowledge that is needed to live well- is central to the UARCTIC consortium and the 4th International Polar Year educational reform effort. A place-based issue oriented context can engage students in chemistry concepts when it intersects with their experience and lives. This article examines the rationale and means of integrating local concerns such as world view, culture, traditional knowledge and policy into both general and specialized chemistry courses. More broadly, capacious place-based issues should be widely adapted by all curriculum reform efforts to demonstrate the connectivity between science and societal understanding of technological options. A case in point is the inclusion of indigenous perspectives in a non-majors general chemistry course when the concepts of scientific method, ice and water resources, genetic engineering, etc. are discussed. In a specialized course on radioactivity in the north, topics connected nuclear chemistry and radioactivity to people and energy. The local landscape should be central to science courses and involve issues relevant to stewardship, a component of the indigenous world view. The historical issues can be connected to current nuclear energy and uranium mining as they relate to the risks and benefits for the local community. This article will make the case that curriculum reform that focuses on real-world topics will not only engage students so that they perform well in class but also spark their interest so that they continue learning after the course is over.

Sled dogs as a model for PM2.5 exposure from wildfires in Alaska.

Particulate matter 2.5 (PM2.5) exposure induces oxidative stress associated with many negative health outcomes such as respiratory disorders, cardiovascular disease and neurodegenerative disease. Research shows that diet and exercise can improve antioxidant defense against oxidative stress. This study is the first to use an Arctic animal model to investigate the cumulative effects of two lifestyle interventions on the antioxidant response before, during, and after ambient PM 2.5 exposure from wildfire: antioxidant supplementation (Arthrospira platensis) and exercise. In a two-factorial, longitudinal design, this study divided sled dogs (n = 48) into four groups (exercise and supplemented, exercise, supplemented, and control) to (1) test the effects of a 30-day exercise and antioxidant supplementation protocol on antioxidant response; and (2) measure the antioxidant response of all groups during and after a natural wildfire event. Commercial assays for total antioxidant power (TAP) and the enzymatic antioxidant superoxide dismutase (SOD) were used as markers for antioxidant status and response. During the forest fire, SOD was increased 5- to 10-fold over pre/post-exposure levels in all groups suggesting an endogenous upregulation of defense systems in response to the acute environmental stress. TAP was lower in all groups at peak PM2.5 exposure compared to 48 h after peak exposure in all groups except the exercise alone group which may indicate that exercise offers improved endogenous defense.

Adaptive response of brain tissue oxygenation to environmental hypoxia in non-sedated, non-anesthetized arctic ground squirrels.

The present study examined the physiological mechanisms of the responses of brain tissue oxygen partial pressure (P(t)O(2)), brain temperature (T(brain)), global oxygen consumption (V(O2)), and respiratory frequency (f(R)) to hypoxia in non-sedated and non-anesthetized arctic ground squirrels (Spermophilus parryii, AGS) and rats. We found that (1) in contrast to oxygen partial pressure in blood (P(a)O(2)), the baseline value of P(t)O(2) in summer euthermic AGS is significantly higher than in rats; (2) both P(t)O(2) and P(a)O(2) are dramatically reduced by inspired 8% O(2) in AGS and rats, but AGS have a greater capacity in P(t)O(2) to cope with environmental hypoxia; (3) metabolic rate before, during, and after hypoxic exposure is consistently lower in AGS than in rats; (4) the respiratory responding patterns to hypoxia in the two species differ in that f(R) decreases in AGS but increases in rats. These results suggest that (1) AGS have special mechanisms to maintain higher P(t)O(2) and lower P(a)O(2,) and these levels in AGS represent a typical pattern of adaptation of heterothermic species to and a brain protection from hypoxia; (2) AGS brain responds to hypoxia through greater decreases in P(t)O(2) and decreased f(R) and ventilation. In contrast, rat brain responds to hypoxia by less reduction in P(t)O(2) and increased f(R) and ventilation.

Resilience and Adaptation: Yukon River Watershed Contaminant Risk Indicators.

River watersheds are among the most complex terrestrial features in Alaska, performing valuable ecosystem functions and providing services for human society. Rivers are vital to both estuarine and aquatic biota and play important roles in biogeochemical cycles and physical processes. The functions of watersheds have been used as vulnerability indicators for ecosystem and socioeconomic resilience. Despite a long history of human activity, the Yukon River has not received the holistic and interdisciplinary attention given to the other great American river systems. By using hypothesis-based monitoring of key watershed functions, we can gain insight to regime-shifting stresses such as fire, toxins, and invasive species development. Coupling adaptive risk management practices involving stakeholders with place-based education, especially contaminants and nutrition related, can maintain resilience within communities. The Yukon watershed provides a broadscale opportunity for communities to monitor the environment, manage resources, and contribute to stewardship policy formation. Monitoring keystone species and community activities, such as citizen science, are critical first steps to following changes to resiliency throughout the Yukon watershed. Creating a policy environment that encourages local experimentation and innovation contributes to resilience maintenance during development-imposed stress.

Exercise Increases Glucose Transporter-4 Levels on Peripheral Blood Mononuclear Cells.

PURPOSE: Glucose transporter 4 (GLUT4) plays a key role in the pathophysiology of type 2 diabetes. Glucose transporter 4 is upregulated in response to exercise, enhancing cellular glucose transport in skeletal muscle tissue. This mechanism appears to remain intact in individuals with insulin resistance. Details of the mechanism are poorly understood and are challenging to study due to the invasive nature of muscle biopsy. Peripheral blood mononuclear cells (PBMC) have documented insulin-sensitive GLUT4 activity and may serve as a proxy tissue for studying skeletal muscle GLUT4. The purpose of this study was to investigate whether GLUT4 in PBMC is affected by conditioning. METHODS: We recruited 16 student athletes from the cross-country running and skiing teams and fifteen sedentary students matched for age and sex from the University of Alaska Fairbanks. Peripheral blood mononuclear cells were collected with mononuclear cell separation tubes. The GLUT4 concentrations were measured using a commercially available enzyme linked immunosorbent assay. Additionally, correlations between PBMC GLUT4 and common indicators of insulin resistance were examined. RESULTS: Results indicate significantly higher PBMC GLUT4 levels in conditioned athletes than in their sedentary counterparts, similar to what has been documented in myocytes. Females were observed to have higher PBMC GLUT4 levels than males. Correlations were not detected between PBMC GLUT4 and hemoglobin A1c, glucose, insulin, homeostatic model assessment of insulin resistance, body mass index, or body fat. CONCLUSIONS: This study provides evidence to support exploration of PBMC as a proxy tissue for studying GLUT4 response to exercise or other noninsulin factors.

Mercury in fishes of Alaska, with emphasis on subsistence species.

In the north, the presence of mercury (Hg) in food leading to chronic exposure is a scientific, economic and political issue. Guidelines have been established for the safe consumption of fish containing Hg, however, adherence to these guidelines must be weighed against the health benefits of consuming fish, such as from the omega-3 polyunsaturated fatty acids, vitamins and minerals. Alaskan Natives generally consume much more fish than the national average. This review summarizes and synthesizes the significant amount of data that has been generated on Hg in Alaska fish, particularly those consumed by Alaskans. Also included are a review of the benefits of eating fish, human health concerns relating to Hg toxicity and various risk assessment guidelines for food consumption. Emphasis was placed on methylmercury (MeHg), the most toxic form to humans. Hg concentrations were examined in 17 freshwater fish species and 24 anadromous and marine fish species, for a total of 2,692 specimens. For freshwater fish the greatest database was on northern pike (Esox lucius). For anadromous and marine fish the greatest database was on Pacific halibut (Hippoglossus stenolepis) and the five species of Pacific salmon (Oncorhynchus spp.). Overall, most fish had muscle Hg concentrations of < or =1 mg kg(-1) (wet wt.), within the USFDA's Action Level and Alaska's guideline for safe concentrations of MeHg in edible fish. Pacific salmon, the most commonly consumed fish group, had exceptionally low (< or =0.1 mg kg(-1)) Hg concentrations. Pacific halibut muscle Hg content was less than 0.3 mg kg(-1). Northern pike, a piscivorous (fish-eating) and long-lived fish, contained the highest muscle Hg values, often exceeding the state's guidelines for food consumption. A discussion of the safe consumption level for pike is included.

Hair analysis in sled dogs (Canis lupus familiaris) illustrates a linkage of mercury exposure along the Yukon River with human subsistence food systems.

The dog has been an important biomedical research model and hair samples from sled dogs could be used as a biomarker of exposure to metals. Hair samples were used as a non-invasive indicator of mercury exposure in sled dogs fed commercial food and traditional village diets. Sled dog populations living in rural New York and Alaska were sampled in 2005 and 2006. Total mercury (THg) content was determined on the entire hair sample in sled dogs from reference sites in North Creek, New York and Salcha Alaska. Both sites fed a commercial feed for high performance dogs and had mean THg levels of 36.6 ng/g for New York sled dogs while Alaskan sled dogs, occasionally supplemented with fish oil showed THg mean of 58.2 ng/g. These THg levels are below levels that are suggested to cause adverse effects and should be considered baseline levels. Yukon River sled dogs had higher THg, ranging from 139 to 15,800 ng/g and showed decreasing mean levels from the delta area to upriver. There were significant differences between THg in the dogs from Russian Mission (10,908.3+/-3028 ng/g), the farthest west village, and Ft. Yukon (1822.4+/-1747 ng/g), the farthest east village. All village dogs along the Yukon had higher THg levels than the THg mean level (657+/-273 ng/g) of hair from ancient dogs of the Seward Peninsula.

Arctic Peoples and Beyond: research opportunities in neuroscience and behaviour.

OBJECTIVES: Arctic and northern peoples are spread across Alaska, Canada, Russia and the Scandinavian countries. Inhabiting a variety of ecosystems, these 4 million residents include Indigenous populations who total about 10% of the population. Although Arctic peoples have very diverse cultural and social systems, they have health issues related to environmental impacts and knowledge/treatment disparities that are common to other minority and Indigenous peoples around the world. Research that explores the neuroscience and behavioural aspects of these health disparities offers challenges and significant opportunities. As the next generation of neuroscientists enter the field, it is imperative that they view their contributions in terms of translational medicine to address health disparities. STUDY DESIGN: A workshop was designed to bring neuroscientists together to report on the current directions of neuroscience research and how it could impact health disparities in the North. This workshop produced research recommendations for the growth of neuroscience in the North. METHODS: On May 31, 2006 the National Institute of Neurological Disorders and Stroke, the Burroughs Wellcome Foundation, the Arctic Division of AAAS and the University of Alaska co-sponsored a workshop entitled "Arctic Peoples and Beyond: Decreasing Health Disparities through Basic and Clinical Research." Also, the role and goals of the International Union for Circumpolar Health (IUCH) were presented at the meeting. RESULTS: A set of recommendations related to research opportunities in neuroscience and behaviour research and ways to facilitate national and international partnerships were developed. CONCLUSIONS: These recommendations should help guide the development of future health research in circumpolar neuroscience and behaviour. They provide ideas about research support and informational exchange that will address health challenges.

Trophic relationships in an Arctic food web and implications for trace metal transfer.

Tissues of subsistence-harvested Arctic mammals were analyzed for silver (Ag), cadmium (Cd), and total mercury (THg). Muscle (or total body homogenates of potential fish and invertebrate prey) was analyzed for stable carbon (delta13C) and nitrogen (delta15N) isotopes to establish trophic interactions within the Arctic food chain. Food web magnification factors (FWMFs) and biomagnification factors for selected predator-prey scenarios (BMFs) were calculated to describe pathways of heavy metals in the Alaskan Arctic. FWMFs in this study indicate that magnification of selected heavy metals in the Arctic food web is not significant. Biomagnification of Cd occurs mainly in kidneys; calculated BMFs are higher for hepatic THg than renal THg for all predator-prey scenarios with the exception of polar bears (Ursus maritimus). In bears, the accumulation of renal THg is approximately 6 times higher than in liver. Magnification of hepatic Ag is minimal for all selected predator-prey scenarios. Though polar bears occupy a higher trophic level than belugas (Delphinapterus leucas), based on delta15N, the metal concentrations are either not statistically different between the two species or lower for bears. Similarly, concentrations of renal and hepatic Cd are significantly lower or not statistically different in polar bears compared to ringed (Phoca hispida) and bearded seals (Erignathus barbatus), their primary prey. THg, on the other hand, increased significantly from seal to polar bear tissues. Mean delta15N was lowest in muscle of Arctic fox (Alopex lagopus) and foxes also show the lowest levels of Hg, Cd and Ag in liver and kidney compared to the other species analyzed. These values are in good agreement with a diet dominated by terrestrial prey. Metal deposition in animal tissues is strongly dependent on biological factors such as diet, age, sex, body condition and health, and caution should be taken when interpreting magnification of dynamic and actively regulated trace metals.

An exploratory study of total mercury levels in archaeological caribou hair from northwest Alaska.

Over the past ten years, total mercury (THg) levels have been surveyed in Alaskan wildlife and fish as part of the Arctic Monitoring and Assessment (AMAP). Beyond these studies there is little historical data on THg levels in important subsistence species for people in Alaska. A survey of THg in caribou hair from archaeological deposits would provide data to develop temporal trends for this region of the Arctic. Caribou hair from a Western Thule settlement beneath the Alaska native village of Deering (ca. AD 1150) show variability in hair THg values, with a mean level (86 ng/g) which is in the range that is observed in modern Rangifer sp. (caribou and reindeer). Hair from House 1 had a THg mean level of 99.6 ng/g and hair from House 2 had a THg mean of 64.2 ng/g. This is the earliest reported record of mercury in caribou associated with human subsistence activities in the western North American Arctic, and is a first step toward compilation of a needed database through which to measure and evaluate exposure to mercury by people who rely heavily on caribou as a food source. We hypothesize that similarity in mercury values in archaeological samples of caribou and in contemporary samples would give an additional perspective on human exposure to mercury through caribou harvest and consumption today. Since this hypothesis will be more useful if evaluated at a regional rather than global scale, further studies will be needed at different archaeological sites across Alaska to determine the generality of this observation in relation to geographic scale.

Stable isotope and trace element status of subsistence-hunted bowhead and beluga whales in Alaska and gray whales in Chukotka.

Tissues of bowhead, beluga, and gray whales were analyzed for Ag, Cd, Cu, Se, Zn, THg and MeHg (belugas only). Delta15N and delta13C in muscle were used to estimate trophic position and feeding habitat, respectively. Trace element concentrations in tissues were significantly different among whale species. Hepatic Ag was higher in belugas than bowheads and gray whales. Gray whales had lower Cd concentrations in liver and kidney than bowhead and belugas and a sigmoid correlation of Cd with length was noted for all whales. Renal and hepatic Se and THg were higher in belugas than in baleen whales. The hepatic molar ratio of Se:THg exceeded 1:1 in all species and was negatively correlated to body length. Hepatic and renal Zn in subsistence-harvested gray whales was lower than concentrations for stranded whales. Se:THg molar ratios and tissue concentrations of Zn may show promise as potential indicators of immune status and animal health.

Mercury concentrations in muscle, brain and bone of Western Alaskan waterfowl.

Total mercury (THg), which includes both inorganic (Hg(2+)) and methylmercury (MeHg) species, has been reported for seabirds in the North Pacific and Alaska. For the Yup'ik and Aleut people of Alaska, waterfowl are a small but important seasonal component of the diet, but many Alaskan species have not been studied extensively for the presence of mercury. Birds are good subjects for examination of mercury concentrations because they feed at different trophic levels, they can be long-lived, and many are both abundant and widely distributed. In this study, we present the levels of mercury in muscle, brain, and bone tissue of 140 birds taken by subsistence food users across Western Alaska. THg wet weight mean concentrations in the 18 species of waterfowl surveyed ranged from 0.8 to 268.6 ng/g in muscle, from 0.4 to 197.7 ng/g in brain and from 0.7 to 422.9 ng/g in bone. The null hypothesis that there are no interspecific differences in the level of total mercury in the 18 species of Alaska birds surveyed was not supported. We found interspecific differences with the Lesser Scaup (Aythya affinis), and the Black Scoter (Melanitta nigra), having the highest muscle tissue levels of THg. In general, THg mean levels were higher in muscle than in brain with the exceptions of the Bar-tailed Godwit and Northern Shoveler. Bone THg were highest in the Black Scoter. The mean values for THg in the species studied are unlikely to cause adverse reproductive or behavioral effects in the birds.

Indoor climate in interior Alaska: simultaneous measurement of ventilation, benzene and toluene in residential indoor air of two homes.

Benzene and toluene mixing ratios were measured in the indoor air of two subarctic homes during summer and winter. Benzene in the living area of these homes ranged from 1 to 25 ppbv and toluene ranged from 1 to 104 ppbv. Source strength estimate calculations supported the hypothesis that gasoline in the home's attached garage is the primary source of these compounds in living area air. These calculations demonstrated that the home with the air-to-air heat exchangers and forced ventilation had less transport of aromatics than the unventilated home. Perturbation experiment showed that a full metal gasoline can in the garage was consistent with the importance of the garage as a source for the concentration of aromatics in the air of the living spaces in these Alaskan homes. The type of ventilation system also had an important effect on the quality of air in the living area.

A note on mercury levels in the hair of Alaskan reindeer.

Reindeer, as terrestrial herbivores, generally have low levels of Hg, but monitoring Hg levels can help in understanding ecological toxicity related to a changing environment. In this study, Alaskan reindeer were analyzed for total mercury (THg) in their hair. Both free-ranging reindeer from the Seward Peninsula, Alaska and reindeer fed a pollock-based fishmeal diet were surveyed. Free ranging reindeer had mean THg levels of (55.3 ng/g; n=5). The mean MeHg level in the free ranging reindeer was 45.5 (ng/g; n=5) or 79% of the THg level. The mean level for THg in the fishmeal fed reindeer was 19 ng/g (n=10). Younger reindeer (2 years of age or less) showed lower levels (0.8 ng/g, n=2) compared to adult reindeer (30.8 ng/g, n=6).

Glucose transporter-4 in white blood cells of young and old sled dogs: a model for human biomarker development.

The insulin responsive glucose transporter, GLUT4 is found predominantly in muscle and adipose cells. Maratou and others (2007) reported that there is GLUT4 in white blood cells (WBC) collected from human subjects in response to insulin activation. This study was designed to validate the presence of GLUT4 in white blood cells of sled dogs and furthermore to investigate whether changes in levels of the GLUT4 protein might be associated with aging. Additionally, we examined the blood insulin concentration of two populations of dogs, young and old, before and after a meal to observe their insulin response. It is documented in skeletal muscle that GLUT4 expression is increased as a result of conditioning, making sled dogs an excellent model in the circumpolar north for studying the effects of exercise, nutrition and diabetes (Felsburg 2002; Kararli 2006). Blood was withdrawn from 11 healthy sled dogs: 6 young (1-5 years) and physically fit, conditioned for racing and 5 old (7-13 years), retired from racing. The insulin response was determined using blood plasma and ELISA. The buffy coat (containing WBC) was collected with a glass pipette after centrifugation and washed and suspended in 1x phosphate buffer. GLUT4 was measured using ELISA kits (USCN Life Sciences). The results validate that GLUT4 is present in white blood cells in sled dogs. Age had no significant effect in the concentration of GLUT4 between the populations of old and young dogs. A significant difference in insulin levels pre and post meal in young (0.13 ± 0.03 ng/mL (pre), 0.22 ± 0.04 ng/mL (post), p < 0.05) and old (0.13 ± 0.02 ng/mL (pre), 0.22 ± 0.03 ng/mL (post), p < 0.05) dogs was observed, displaying the typical postprandial insulin spike. No significant difference was found in insulin concentration comparing old versus young dogs. Our data shows that white blood cells in young (40.4 ± 2.4 ng/mL) and old (35.3 ± 8.8 ng/mL) sled dogs have quantifiable but non-significant different GLUT4 levels (p > 0.05). Detecting GLUT4 via an ELISA in white blood cells, opens up minimally invasive avenues for studying the underlying molecular mechanisms associated with insulin resistance in more complex, dynamic and physiological systems. This project was the first step in developing a protocol for this simple, technique with a potential clinical application for diagnosing insulin resistance.

The effect of acute exercise on GLUT4 levels in peripheral blood mononuclear cells of sled dogs.

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 24h 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 24h 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 24h 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.