Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Relationship between red blood cell lifespan and endogenous carbon monoxide in the common bottlenose dolphin and beluga

Certain deep-diving marine mammals (i.e., northern elephant seal (Mirounga angustirosis), Weddell seal (Leptonychotes weddellii)) have blood carbon monoxide (CO) levels that are comparable to those of chronic cigarette smokers. Most CO produced in humans is a by-product of heme degradation, which is released when red blood cells (RBC) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy, marine mammal species with different diving capacities and heme stores, the shallow diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga (Delphinapterus leucas) and relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared to humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared to humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long duration breath-holds

Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation A serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial

ObjectivesThe aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effects of polymer-based, paclitaxel-eluting stents on in-stent neointima formation and late incomplete stent apposition.BackgroundThe TAXUS-IV trial demonstrated that the slow-release, polymer-based, paclitaxel-eluting stent reduces angiographic restenosis and the need for repeat revascularization procedures. Serial IVUS studies reveal details of the pattern of vascular responses provoked by stent implantation that provide insight into device safety and efficacy.MethodsIn the TAXUS-IV trial, patients were randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). As part of a formal substudy, complete volumetric IVUS data were available in 170 patients, including 88 TAXUS patients and 82 controls, at implantation and at nine-month follow-up.ResultsNo baseline differences were present in the clinical characteristics or IVUS parameters between the control and TAXUS groups. At nine-month follow-up, IVUS lumen volumes were larger in the TAXUS group (123 ± 43 mm3vs. 104 ± 44 mm3, p = 0.005), due to a reduction in neointimal volume (18 ± 18 mm3vs. 41 ± 23 mm3, p < 0.001). Millimeter-by-millimeter analysis within the stent demonstrated uniform suppression of neointimal growth along the entire stent length. Late lumen loss was similar at the proximal edge of the stent between the two groups, and reduced with the TAXUS stent at the distal edge (p = 0.004). Incomplete stent apposition at nine months was observed in only 3.0% of control and 4.0% of TAXUS stents (p = 0.12).ConclusionsPolymer-based, paclitaxel-eluting TAXUS stents are effective in inhibiting neointimal tissue proliferation, and do not result in late incomplete stent apposition

Development Enhances Hypometabolism and the Dive Response in Northern Elephant Seal Pups (Mirounga Angustirostris)

Purpose of the Study:\ud Several studies have investigated the development of oxygen storage capacity in diving animals, but few studies have examined the development of oxygen store usage in these animals. Northern elephant seals (Mirounga angustirostris) are known to be air-breathing marine predators which exhibit continuous, long-duration, deep dives in the pelagic Pacific Ocean. Despite several previous attempts to calculate the duration allotted towards diving in an aerobic state, these animals consistently surpass this diving duration and repeatedly exhibit short surface intervals between dives. This information, suggests these animals are dramatically reducing their oxygen consumption (V02) during diving, compared to the V02 data used to predict aerobic dive durations.\ud Additionally, little work has been done investigating the development of the "dive response" in marine mammals. This basic, physiological response to breath-holding and submersion allow individuals to achieve a greater reduction in V02??? Information regarding the developmental aspects of this diving response in concert with an understanding on V02 reductions during a diving state can assist in understanding the energetic demands and processes these animals face.\ud The purpose of this study is to determine the role of development on; a) the diving response and b) the ability to reduce V02 during breath-holds.Procedure:\ud To determine the role of development on both the diving response and VOl during breath-holds, this study investigated V02 and blood-gas use during voluntary rest-associated apneas and voluntary submergences in 17 weaned northern elephant seal pups. Pups were either early in their weaning period (2 weeks post weaning) or late in their weaning period (7 weeks post weaning). Standard blood gas analysis and flow-through respirometry were used during both breath-hold types.\ud Findings:\ud When compared to early-weaned animals, there was a mean reduction of 17% in V02 during the\ud breath-holds of older animals. This suggests a large role in the developmental period on the\ud ability to reduce oxygen consumption during breath-holds in northern elephant seals. The\ud maximum reduction of breath-hold V02 from resting VOl was a 53% reduction, seen in an older\ud animal. Blood-oxygen depletion rates during submergences occurred 24% slower, when\ud compared to rest-associated apneas. Additionally, pC02 values obtained from the end of breathholds\ud were statistically similar across durations and between sexes, ages and breath-hold type.\ud This implies the final pC02 value of 59 ?? 5.8 mmHg during a breath-hold, is the value which\ud triggers chemoreceptors to initiate breathing and terminate the breath-hold.Conclusions:\ud The developmental period in northern elephant seals is a critical time frame in which the animals\ud build O2 stores and enhance their ability to utilize these stores in a manner which extends the\ud time they spend in an aerobic state. This will allow these air-breathing predators to prolong\ud their dive durations at sea and condense the time at the surface needed to clear anaerobic\ud byproducts, resulting in more time available for foraging and less time available exposed to\ud surface-predators

Lessons in immune adaptations to hypoxia revealed by comparative and evolutionary physiology

Recent findings from comparative and evolutionary physiologists reveal novel insights into the regulation of inflammation and immune function under conditions of chronic-sustained and intermittent hypoxia. Comparative approaches provide a valuable gateway for discovering essential principals of physiology and adaptive molecular strategies utilized in nature that protect against clinically relevant stressors, which can guide therapeutic developments in biomedical science

Isolation of progenitor cells from the blubber of northern elephant seals (mirounga angustirostris) in order to obtain an in vitro adipocyte model-preliminary results

Marine top predators are highly informative in understanding the quality and health of ocean habitats. Through bioamplification, they face a very large risk of exposure to toxic, persistent, and fat-soluble molecules such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodimethyltrichloroethane (DDT), and methylmercury, which are preferentially stored in the adipose tissue. The life history of pinnipeds often includes extended periods of fasting on land. This is particularly true for phocid seals such as northern elephant seal (NES) (Mirounga angustirostris). This species indeed exhibits one of the most extreme terrestrial fasting durations (up to 3 mo) corresponding to breeding, lactation, and molting for females, postweaning development for pups, and maintaining a territory or competing for dominance rank on the breeding rookery for males (Le Boeuf et al. 1972). During such periods, individuals mobilize primarily lipids from their large adipose tissue stores (Costa et al. 1986, Noren et al. 2003). This mobilization of blubber lipids presents a risk through the release of environmental pollutants into the circulation. Previous studies in fasting NES pups and females elucidated the mobilization dynamic

Supplementary materials: Expanded analyses from The extra burden of motherhood: reduced dive duration associated with pregnancy status in a deep-diving mammal, the northern elephant seal

The cost of pregnancy is hard to study in marine mammals, particularly in species that undergo pregnancy while diving continuously at sea such as elephant seals (genus <i>Mirounga</i>). We analysed the diving behaviour of confirmed pregnant and non-pregnant northern elephant seals (<i>M. angustirostris</i>, <i>n</i> = 172) and showed that after an initial continuous increase in dive duration, dives of pregnant females become shorter after week 17. The reasons for this reduction in dive duration remain unknown, but we hypothesize that increased fetal demand for oxygen could be the cause. Our findings reveal an opportunity to explore the use of biologging data to investigate pregnancy status of free-ranging marine mammals and factors that could affect pregnancy success