The lunar cycle drives migration of a nocturnal bird.

Every year, billions of seasonal migrants connect continents by transporting nutrients, energy, and pathogens between distant communities and ecosystems. For animals that power their movements by endogenous energy stores, the daily energy intake rates strongly influence the speed of migration. If access to food resources varies cyclically over the season, migrants sensitive to changes in daily energy intake rates may adjust timing of migration accordingly. As an effect, individuals adjusting to a common temporal cycle are expected to approach synchrony in foraging and movement. A large-scale periodic pattern, such as the dark-light cycle of the moon, could thus synchronize migrations across animal populations. However, such cyclic effects on the temporal regulation of migration has not been considered. Here, we show the temporal influence of the lunar cycle on the movement activity and migration tactics in a visual hunting nocturnal insectivore and long-distance migrant, the European nightjar, Caprimulgus europeaus. We found that the daily foraging activity more than doubled during moonlit nights, likely driven by an increase in light-dependent fuelling opportunities. This resulted in a clear cyclicity also in the intensity of migratory movements, with occasionally up to 100% of the birds migrating simultaneously following periods of full moon. We conclude that cyclic influences on migrants can act as an important regulator of the progression of individuals and synchronize pulses of migratory populations, with possible downstream effects on associated communities and ecosystems.

Flight altitude dynamics of migrating European nightjars across regions and seasons.

Avian migrants may fly at a range of altitudes, but usually concentrate near strata where a combination of flight conditions is favourable. The aerial environment can have a large impact on the performance of the migrant and is usually highly dynamic, making it beneficial for a bird to regularly check the flight conditions at alternative altitudes. We recorded the migrations between northern Europe and sub-Saharan Africa of European nightjars Caprimulgus europaeus to explore their altitudinal space use during spring and autumn flights and to test whether their climbs and descents were performed according to predictions from flight mechanical theory. Spring migration across all regions was associated with more exploratory vertical flights involving major climbs, a higher degree of vertical displacement within flights, and less time spent in level flight, although flight altitude per se was only higher during the Sahara crossing. The nightjars commonly operated at ascent rates below the theoretical maximum, and periods of descent were commonly undertaken by active flight, and rarely by gliding flight, which has been assumed to be a cheaper locomotion mode during descents. The surprisingly frequent shifts in flight altitude further suggest that nightjars can perform vertical displacements at a relatively low cost, which is expected if the birds can allocate potential energy gained during climbs to thrust forward movement during descents. The results should inspire future studies on the potential costs associated with frequent altitude changes and their trade-offs against anticipated flight condition improvements for aerial migrants.

Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.

Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of ß-cells of the pancreatic islets of Langerhans. It is a regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets. It has binding sites in the brain, possibly contributing also to satiety regulation and inhibits gastric emptying. Effects on several other organs have also been described. IAPP was discovered through its ability to aggregate into pancreatic islet amyloid deposits, which are seen particularly in association with type 2 diabetes in humans and with diabetes in a few other mammalian species, especially monkeys and cats. Aggregated IAPP has cytotoxic properties and is believed to be of critical importance for the loss of ß-cells in type 2 diabetes and also in pancreatic islets transplanted into individuals with type 1 diabetes. This review deals both with physiological aspects of IAPP and with the pathophysiological role of aggregated forms of IAPP, including mechanisms whereby human IAPP forms toxic aggregates and amyloid fibrils.

Actogram analysis of free-flying migratory birds: new perspectives based on acceleration logging.

The use of accelerometers has become an important part of biologging techniques for large-sized birds with accelerometer data providing information about flight mode, wing-beat pattern, behaviour and energy expenditure. Such data show that birds using much energy-saving soaring/gliding flight like frigatebirds and swifts can stay airborne without landing for several months. Successful accelerometer studies have recently been conducted also for free-flying small songbirds during their entire annual cycle. Here we review the principles and possibilities for accelerometer studies in bird migration. We use the first annual actograms (for red-backed shrike Lanius collurio) to explore new analyses and insights that become possible with accelerometer data. Actogram data allow precise estimates of numbers of flights, flight durations as well as departure/landing times during the annual cycle. Annual and diurnal rhythms of migratory flights, as well as prolonged nocturnal flights across desert barriers are illustrated. The shifting balance between flight, rest and different intensities of activity throughout the year as revealed by actogram data can be used to analyse exertion levels during different phases of the life cycle. Accelerometer recording of the annual activity patterns of individual birds will open up a new dimension in bird migration research.

Solar heating may explain extreme diel flight altitude changes in migrating birds.

Great reed warblers, Acrocephalus arundinaceus,1 and great snipes, Gallinago media,2 exhibit a diel cycle in flight altitudes-flying much higher during the day than the night-when performing migratory flights covering both night and day. One hypothesis proposed to explain this behavior is that the birds face additional heating by solar radiation during daytime and hence must climb to very high, and thus also very cold, altitudes to avoid overheating during daytime flights.1,2 Yet, solar heat gain in birds has been shown to drastically decrease with wind speed,3,4 and the quantitative heating effect by solar radiation on a bird flying with an airspeed of 10 m/s or more is unknown. We analyzed temperature data from multisensor data loggers (MDLs)5,6 placed without direct exposure to solar radiation on great reed warblers (the logger covered by feathers on the back) and great snipes (the logger on the leg, covered from the sun by the tail). We found that logger temperatures were significantly higher (5.9°C-8.8°C in great reed warblers and 4.8°C-5.4°C in great snipes) during the day than during the night in birds flying at the same altitudes (and thus also the same expected ambient air temperatures). These results strongly indicate that the heat balance of the flying birds is indeed affected by solar radiation, which is in accordance with the hypothesis that solar radiation is a key factor causing the remarkable diel cycles in flight altitude observed in these two long-distance migrant bird species.1,2.

Activity patterns throughout the annual cycle in a long-distance migratory songbird, the red-backed shrike Lanius collurio.

BACKGROUND: Long-distance migratory birds undergo complex annual cycles during which they must adjust their behaviour according to the needs and conditions encountered throughout the year. Yet, variation in activity throughout the entire annual cycle has rarely been studied in wild migratory birds. METHODS: We used multisensor data loggers to evaluate the patterns of activity throughout the complete annual cycle of a long-distance migratory bird, the red-backed shrike Lanius collurio. Accelerometer data was used to identify life-history stages and to estimate levels of activity during various phases of the annual cycle. In this study, we analysed the variation in daytime activity along the annual cycle and between migratory and non-migratory days. RESULTS: The birds' daytime activity varied throughout the annual cycle while night-time activity was almost exclusively restricted to migratory flights. The highest daytime activity levels were observed during the breeding season, while it remained low during autumn migration and the winter period. Daytime activity differed between sexes during the breeding period, when the males showed the highest level in activity. During migratory periods, both sexes exhibited a higher daytime activity in spring compared to autumn migration, being particularly high in the final migratory leg towards the breeding ground. The birds showed a lower daytime activity on migratory days (days when a migratory flight took place during the succeeding night) than on non-migratory days during both migratory seasons. CONCLUSIONS: Activity measured during daytime results from a combination of several behaviours, and a high daytime activity during spring migration and the breeding period is possibly reflecting particularly energy-demanding periods in the annual cycle of migratory birds. The use of multisensor data loggers to track annual activity provides us with a full annual perspective on variation in activity in long-distance migratory species, an essential approach for understanding possible critical life-history stages and migration ecology.

Extreme altitudes during diurnal flights in a nocturnal songbird migrant.

Billions of nocturnally migrating songbirds fly across oceans and deserts on their annual journeys. Using multisensor data loggers, we show that great reed warblers (Acrocephalus arundinaceus) regularly prolong their otherwise strictly nocturnal flights into daytime when crossing the Mediterranean Sea and the Sahara Desert. Unexpectedly, when prolonging their flights, they climbed steeply at dawn, from a mean of 2394 meters above sea level to reach extreme cruising altitudes (mean 5367 and maximum 6267 meters above sea level) during daytime flights. This previously unknown behavior of using exceedingly high flight altitudes when migrating during daytime could be caused by diel variation in ambient temperature, winds, predation, vision range, and solar radiation. Our finding of this notable behavior provides new perspectives on constraints in bird flight and might help to explain the evolution of nocturnal migration.

Extreme altitude changes between night and day during marathon flights of great snipes.

Several factors affect the flight altitude of migratory birds, such as topography, ambient temperature, wind conditions, air humidity, predation avoidance, landmark orientation, and avoiding over-heating from direct sunlight.1-6 Recent tracking of migratory birds over long distances has shown that migrants change flight altitude more commonly and dramatically than previously thought.4-8 The reasons behind these altitude changes are not well understood. In their seasonal migrations between Sweden and sub-Saharan Africa, great snipes Gallinago media make non-stop flights of 4,000-7,000 km, lasting 60-90 h.9,10 Activity and air pressure data from multisensor dataloggers showed that great snipes repeatedly changed altitudes around dawn and dusk, between average cruising heights about 2,000 m (above sea level) at night and around 4,000 m during daytime. Frequency and autocorrelation analyses corroborated a conspicuous diel cycle in flight altitude. Most birds regularly flew at 6,000 m and one bird reached 8,700 m, possibly the highest altitude ever recorded for an identified migrating bird. The diel altitude changes took place independently of climate zone, topography, and habitat overflown. Ambient temperature, wind condition, and humidity have no important diel variation at the high altitudes chosen by great snipes. Instead, improved view for orientation by landmarks, predator avoidance, and not least, seeking cold altitudes at day to counteract heating from direct sunlight are the most plausible explanations for the diel altitude cycle. Together with similar recent findings for a small songbird,6 the great snipes' altitudinal performance sheds new light on the complexity and challenges of migratory flights.

Growth hormone increases beta-cell proliferation in transplanted human and fetal rat islets.

OBJECTIVE: The aim of the study was to increase the number of human islet beta-cells after transplantation with injections of human growth hormone (hGH). INTERVENTIONS: Human islets and fetal rat islets were transplanted under the left kidney capsule and under the right kidney capsule, respectively in nude normoglycemic mice which were then given a daily injection of 200 microg hGH for 1-4 weeks. MAIN OUTCOME MEASURE: Beta-cell proliferation was determined using thymidine incorporation and the beta-cell area was assessed using light microscopy. RESULTS: Mice given hGH increased their body weight one week after transplantation and had a more efficient removal of glucose after 3 and 4 weeks. Treatment with hGH resulted in increased beta-cell proliferation in human and fetal rat beta-cells, and the beta-cell area tended to increase. However, serum insulin concentrations and pancreas insulin content remained unchanged. CONCLUSIONS: hGH increased the proliferation of transplanted human beta-cells as well as improving the glucose tolerance of the transplanted mice.

Transient beneficial effects of exendin-4 treatment on the function of microencapsulated mouse pancreatic islets.

Transplantation of microencapsulated islets may reduce hyperglycemia in the absence of immunosuppression. However, the efficiency of microencapsulated islet transplantation is low, requiring more islets to achieve normoglycemia than in vascularized islet transplantation. Exendin-4 (a glucagon-like receptor agonist) has been previously shown to improve islet transplantation outcome in rodents. We investigated whether this treatment would enhance the function of microencapsulated islets in vitro and in vivo. Encapsulated or naked islets were cultured with or without exendin-4 for 72 h. To test in vitro function, insulin release and glucose oxidation rates were measured in the absence or presence of exendin-4. In addition, in vivo function of a minimal mass of 350 microencapsulated islets was assessed by syngeneic transplantation into the peritoneal cavity of alloxan-diabetic mice. Glucose oxidation rates of microencapsulated islets were improved by 72-h pretreatment with exendin-4. Insulin release was increased both acutely after glucose stimulation and over a 40-h culture period by the presence of exendin-4. Transplantation outcome of microencapsulated islets cultured with exendin-4 was initially improved, but by day 7 there were no differences compared with control cultured microencapsulated islets. Culture of microencapsulated islets with exendin-4 increases glucose oxidation and insulin release rates, but the increased function seen in vitro was not enough to improve the long term outcome in a transplantation model.

Distribution of intraportally implanted microspheres and fluorescent islets in mice.

The aim of the study was to evaluate the distribution of intraportally transplanted islets in mice. We initially administered 2000 polystyrene microspheres with a diameter of 50 microm intraportally into normoglycemic C57BL/6 mice. In separate experiments other mice were injected similarly with 300 microspheres each with a diameter of 100 or 200 microm. One week later the animals were killed, and the lungs and livers were removed and divided into lobes. The number of microspheres in each individual liver lobe and in the lungs was counted using a stereomicroscope. In other experiments, athymic C57BL/6 mice were similarly implanted with 250 islets isolated from transgenic mice expressing the enhanced yellow fluorescent protein in the islet cells. The distribution of microspheres and islets was independent of size, and fairly homogenous within the liver, with the exception of the caudate lobe, which contained fewer microspheres and islets, respectively. Approximately one third of all microspheres and islets were present as aggregates. Eighty-five to 90% of the implanted microspheres were identified in the liver sections, whereas 60-65% of the implanted islets were recovered. Aggregates or single fluorescent cells were observed in the liver of islet-implanted mice. We conclude that islets and microspheres implanted into the liver distribute fairly homogenously and quite a few of them exist as aggregates or, with respect to islets, as fragments.

Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats.

The growth of both tumors and nonneoplastic tissues may be influenced by signals from the vascular endothelium. In the present investigation we show that purified proliferating endothelial cells from pancreatic islets can stimulate beta-cell proliferation through secretion of hepatocyte growth factor (HGF). This secretion could be induced by soluble signals from the islets, such as vascular endothelial growth factor-A (VEGF-A) and insulin. During pregnancy, the pancreatic beta-cells display a highly reproducible physiological proliferation. We show that islet endothelial cell proliferation precedes beta-cell proliferation in pregnant animals. Vascular growth was closely associated with endocrine cell proliferation, and prominent expression of HGF was observed in islet endothelium on d 15 of pregnancy, i.e. coinciding with the peak of beta-cell proliferation. In summary, our results suggest the existence of an endothelial-endocrine axis within adult pancreatic islets, which is of importance for adult beta-cell proliferation.

No differences in efficacy between noncultured and cultured islets in reducing hyperglycemia in a nonvascularized islet graft model.

BACKGROUND: Although islet transplantation is a promising method to restore normoglycemia in recipients with diabetes, large numbers of pancreatic islets are still needed. It has been suggested that the use of freshly isolated islets could improve transplantation outcome through better vascular engraftment. Using a technique of microencapsulation, a model where revascularization is not possible, we investigated the importance of revascularization for transplantation outcome. METHODS: Either 700 or 350 3-day-cultured or noncultured encapsulated islets were transplanted intraperitoneally into syngeneic mice with alloxan-induced diabetes. In addition, 700 nonencapsulated islets were transplanted to mice with diabetes. Blood glucose concentrations were monitored, and glucose tolerance tests were carried out. After 42 days, the encapsulated islets were retrieved and assayed for glucose oxidation and insulin release rates. RESULTS: There were no differences between capsules containing fresh or cultured islets in their capacity to lower the blood glucose concentration of the recipients or in the in vitro function after capsule retrieval. Interestingly, mice that were intraperitoneally transplanted with 700 encapsulated islets had average blood glucose levels well below 11 mM for most of the study, whereas the same number of nonencapsulated islets had no beneficial effects on the blood glucose homeostasis. CONCLUSIONS: Encapsulated islets can reverse hyperglycemia after transplantation to the intraperitoneal site. This effect was not seen when nonencapsulated islets were grafted. Since a 3- day culture period did not influence the outcome of transplantation of encapsulated islets there is evidence to suggest that a more appropriate revascularization may explain why freshly isolated islets are more efficient than cultured islets.

Annual 10-Month Aerial Life Phase in the Common Swift Apus apus.

The common swift (Apus apus) is adapted to an aerial lifestyle, where food and nest material are captured in the air. Observations have prompted scientists to hypothesize that swifts stay airborne for their entire non-breeding period [1, 2], including migration into sub-Saharan Africa [3-5]. It is mainly juvenile common swifts that occasionally roost in trees or buildings before autumn migration when weather is bad [1, 6]. In contrast, the North American chimney swift (Chaetura pelagica) and Vaux's swift (C. vauxi) regularly settle to roost in places like chimneys and buildings during migration and winter [7, 8]. Observations of common swifts during the winter months are scarce, and roost sites have never been found in sub-Saharan Africa. In the breeding season, non-breeding individuals usually spend the night airborne [9], whereas adult nesting birds roost in the nest [1]. We equipped common swifts with a micro data logger with an accelerometer to record flight activity (years 1-2) and with a light-level sensor for geolocation (year 2). Our data show that swifts are airborne for >99% of the time during their 10-month non-breeding period; some individuals never settled, but occasional events of flight inactivity occurred in most individuals. Apparent flight activity was lower during the daytime than during the nighttime, most likely due to prolonged gliding episodes during the daytime when soaring in thermals. Our data also revealed that twilight ascents, previously observed during the summer [10], occur throughout the year. The results have important implications for understanding physiological adaptations to endure prolonged periods of flight, including the need to sleep while airborne.

Evidence of functional impairment of syngeneically transplanted mouse pancreatic islets retrieved from the liver.

A drawback in pancreatic islet transplantation is the large number of islets needed to obtain insulin independence in patients with diabetes. This most likely reflects extensive posttransplantation islet cell death and functional impairment of the remaining endocrine cells. We aimed to develop an experimental method to retrieve transplanted islets from the mouse liver, which would enable comparisons of transplanted and endogenous islets and provide valuable information on functional changes induced by intraportal transplantation. Transplanted islets were obtained by retrograde perfusion of the liver with collagenase. The identity of retrieved tissue as transplanted islets was confirmed by intravital staining, immunohistochemistry, and electron microscopy. The retrieved islets, irrespective of whether they had resided in diabetic or nondiabetic recipients, had a markedly lower insulin content and glucose-stimulated insulin release when compared with isolated endogenous islets. The glucose oxidation rate was also markedly lower in the retrieved islets, suggesting mitochondrial dysfunction. These disturbances in insulin content, insulin release, and glucose oxidation rate were not reversed by a few days of culture after retrieval. The results implicate changes in islet function after intraportal transplantation. Such dysfunction may contribute to the high number of islets needed for successful transplantation in diabetic individuals.

Pancreatic islet function in a transgenic mouse expressing fluorescent protein.

Pancreatic islet function and glucose homeostasis have been characterized in the transgenic YC-3.0 mouse, which expresses the yellow chameleon 3.0 (YC-3.0) protein under the control of the beta-actin and the cytomegalovirus promoters. Fluorescence from the enhanced yellow fluorescent protein (EYFP), one part of the yellow chameleon protein, was used as a reporter of transgene expression. EYFP was expressed in different quantities throughout most cell types, including islet endocrine and stromal cells. No adverse effects of the transgene on animal health, growth or fertility were observed. Likewise, in vivo glucose homeostasis, mean arterial blood pressure and regional blood flow values were normal. Furthermore, the transgenic YC-3.0 mouse had a normal beta-cell volume and mass as well as glucose-stimulated insulin release in vitro, compared with the C57BL/6 control mouse. Isolated islets from YC-3.0 animals continuously expressed the transgene and reversed hyperglycemia when transplanted under the renal capsule of alloxan-diabetic nude mice. We conclude that isolated pancreatic islets from YC-3.0 animals implanted into recipients without any EYFP expression, constitute a novel and versatile model for studies of islet engraftment.

Duct ligation and pancreatic islet blood flow in rats: physiological growth of islets does not affect islet blood perfusion.

OBJECTIVES: The aim of this study was to evaluate islet blood-flow changes during stimulated growth of the islet organ without any associated functional impairment of islet function. DESIGN: A duct ligation encompassing the distal two-thirds of the pancreas was performed in adult, male Sprague-Dawley rats. METHODS: Pancreatic islet blood flow was measured in duct-ligated and sham-operated rats 1, 2 or 4 weeks after surgery. In some animals studied 4 weeks after surgery, islet blood flow was also measured also during hyperglycaemic conditions. RESULTS: A marked atrophy of the exocrine pancreas was seen in all duct-ligated rats. Blood glucose and serum insulin concentrations were normal. An increased islet mass was only seen 4 weeks after surgery. No differences in islet blood perfusion were noted at any time point after duct ligation. In both sham-operated and duct-ligated rats islet blood flow was increased during hyperglycaemia; the response was, however, slightly more pronounced in the duct-ligated part of the gland. CONCLUSIONS: Normal, physiological islet growth does not cause any major changes in the islet blood perfusion or its regulation. This is in contrast to findings during increased functional demands on the islets or during deteriorated islet function, when increased islet blood flow is consistently seen.

Blood glucose-lowering activity of a hyaluronan-insulin complex after oral administration to rats with diabetes.

BACKGROUND: Several covalently modified insulin derivatives or formulations with absorption enhancers have been shown to decrease the blood glucose concentration after oral administration in animals with diabetes. The aim of this study was to investigate the biological activity of a novel hyaluronan-insulin complex. METHODS: The efficacy of the complexed insulin after oral and subcutaneous administration was evaluated by analysis of blood glucose concentrations in rats with streptozotocin-induced diabetes. RESULTS: The complexed insulin significantly decreased blood glucose concentrations within 1 h after oral administration in eight of 10 rats in the dose interval 1.5-4.7 mg (3.1-14.5 mg/kg). Oral administration of native insulin or non-complexed insulin plus hyaluronan using similar doses failed to decrease blood glucose concentrations. The lowest oral dose of complexed insulin achieving a statistically significant decrease in blood glucose concentrations was 1.2-1.5 mg (about 4 mg/kg), and the threshold dose after subcutaneous administration was 0.08-0.12 mg (0.25 mg/kg). CONCLUSIONS: The hyaluronan-insulin complex was active after oral administration and decreased blood glucose concentrations in rats with streptozotocin-induced diabetes. The ratio between the oral and subcutaneous threshold doses was about 16.

Changes in intracellular sodium, potassium, and calcium concentrations in transplanted mouse pancreatic islets.

BACKGROUND: Our previous studies have suggested a chronically low oxygen tension in transplanted pancreatic islets. The present study tested the hypothesis that this may be coupled to changes in intracellular concentrations of crucial ions within the transplanted islet cells and, thus, their function. METHODS: X-ray microanalysis was used for studies of native islet cells and islet grafts residing for 1 day or 1 month in nondiabetic or diabetic recipients. RESULTS: Markedly increased sodium concentrations and decreased potassium concentrations were recorded in all transplanted islet cells, irrespective of whether the grafts had been implanted into nondiabetic or diabetic recipients or whether they were investigated 1 day or 1 month after transplantation. The calcium concentration in 1-day-old islet grafts was similar to that in native islet cells, but it decreased markedly between 1 day and 1 month after transplantation. Again this was seen in both nondiabetic and diabetic recipients. CONCLUSIONS: Most probably, the disturbances in graft sodium and potassium concentrations reflect ATP depletion and inhibition of the Na/K-ATPase in the plasma membrane as a result of impeded oxygen supply. The decreased calcium concentrations developing over time in the transplanted islet cells might be potentially detrimental, because calcium plays a fundamental role in the control of a variety of cellular functions, including insulin secretion, in beta cells.