Amylin in the periphery II: An updated mini-review

Amylin is a polypeptide that is cosecreted with insulin from the beta cells of the pancreas. Therefore, in states of diabetes in which the beta-cell mass is largely depleted or dysfunctional, insulin and amylin secretion are also lost or dysregulated. While the soluble monomeric form of amylin acts as a hormone that alters physiological responses related to feeding and acts as a specific growth factor, there has been renewed interest in the less-soluble oligomeric and insoluble polymeric forms of human (also monkey and cat) amylin that may contribute to the establishment of a pathophysiological pathway to overt diabetes. With this discovery has grown the hope of minimizing, with appropriate therapy, these toxic forms to preserve the functional (c) not-cell mass. Human beta cells may also be more vulnerable to these forms and one risk factor, a higher fat diet, may promote toxic forms. The generation and utilities of transgenic rodent models, which express enhanced levels of human amylin, have been accompanied by strategies that may lead to the reduction of toxic forms and associated risk factors. The successful definition and faithful expression of the physiological receptors (and complexes) for amylin that may differ for each target organ is an important development in the field of amylin research generally. Besides the heuristic value for the understanding of the molecular biology of receptors, the opportunity to screen and identify nonpeptide analogues that bind the physiological receptors has important implications for biomedicine and clinical practice in relation to treatments for diabetic complications, bone diseases, and eating disorders. In particular, in their capacities to mimic the effects of amylin as a growth factor, amylin analogues may prove useful in the stimulation of beta-cell mass (in conjunction with other factors), reduce the activity of the osteoclast population, and stimulate the regeneration of proximal tubules following toxic insult (and thus avoid the development of renal insufficiency)

Peripheral Calcitonin Gene-Related Peptide Receptor Activation and Mechanical Sensitization of the Joint in Rat Models of Osteoarthritis Pain

OBJECTIVE: To investigate the role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in peripheral sensitization in experimental models of osteoarthritis (OA) pain. METHODS: Experimental knee OA was induced in rats by intraarticular injection of monosodium iodoacetate (MIA) or by transection of the medial meniscus (MMT). Single-unit recordings of joint-innervating nociceptors were obtained in MIA- and saline-treated rats following administration of CGRP or the CGRP receptor antagonist CGRP 8-37. Effects of CGRP 8-37 were also examined in rats that underwent MMT and sham operations. Protein and messenger RNA (mRNA) levels of CGRP receptor components in the L3-L4 dorsal root ganglion (DRG) were investigated following MIA treatment. RESULTS: In both the MIA and MMT groups, the mechanical sensitivity of joint nociceptors was enhanced compared to that in the control groups. Exogenous CGRP increased mechanical sensitivity in a greater proportion of joint nociceptors in the MIA-treated rats than in the saline-treated rats. Local blockade of endogenous CGRP by CGRP 8-37 reversed both the MIA- and MMT-induced enhancement of joint nociceptor responses. Joint afferent cell bodies coexpressed the receptor for CGRP, called the calcitonin-like receptor (CLR), and the intracellular accessory CGRP receptor component protein. MIA treatment increased the levels of mRNA for CLR in the L3-L4 DRG and the levels of CLR protein in medium and large joint afferent neurons. CONCLUSION: Our findings provide new and compelling evidence implicating a role of CGRP in peripheral sensitization in experimental OA. Our novel finding of CGRP-mediated control of joint nociceptor mechanosensitivity suggests that the CGRP receptor system may be an important target for the modulation of pain during OA. CGRP receptor antagonists recently developed for migraine pain should be investigated for their efficacy against pain in OA

Effects of Warming on Shrub Abundance and Chemistry Drive Ecosystem-Level Changes in a Forest-Tundra Ecotone

Tundra vegetation is responding rapidly to on-going climate warming. The changes in plant abundance and chemistry might have cascading effects on tundra food webs, but an integrated understanding of how the responses vary between habitats and across environmental gradients is lacking. We assessed responses in plant abundance and plant chemistry to warmer climate, both at species and community levels, in two different habitats. We used a long-term and multisite warming (OTC) experiment in the Scandinavian forest–tundra ecotone to investigate (i) changes in plant community composition and (ii) responses in foliar nitrogen, phosphorus, and carbon-based secondary compound concentrations in two dominant evergreen dwarf-shrubs (Empetrum hermaphroditum and Vaccinium vitis-idaea) and two deciduous shrubs (Vaccinium myrtillus and Betula nana). We found that initial plant community composition, and the functional traits of these plants, will determine the responsiveness of the community composition, and thus community traits, to experimental warming. Although changes in plant chemistry within species were minor, alterations in plant community composition drive changes in community-level nutrient concentrations. In view of projected climate change, our results suggest that plant abundance will increase in the future, but nutrient concentrations in the tundra field layer vegetation will decrease. These effects are large enough to have knock-on consequences for major ecosystem processes like herbivory and nutrient cycling. The reduced food quality could lead to weaker trophic cascades and weaker top down control of plant community biomass and composition in the future. However, the opposite effects in forest indicate that these changes might be obscured by advancing treeline forests

Whole-crown 13C-pulse labelling in a sub-arctic woodland to target canopy-specific carbon fluxes

Climate change-driven increases in plant productivity have been observed at high northern latitudes. These trends are driven, in part, by the increasing abundance of tall shrub and tree species in arctic ecosystems, and the advance of treelines. Higher plant productivity may alter carbon (C) allocation and, hence, ecosystem C cycling and soil C sequestration. It is important to understand the contributions that the newly established canopy forming overstorey species makes to C cycling in these ecosystems. However, the presence of a dense understorey cover makes this challenging, with established partitioning approaches causing disturbance and potentially introducing measurement artefacts. Here, we develop an in situ whole-crown 13C-pulse labelling technique to isolate canopy C fluxes in areas of dense understorey cover. The crowns of five mountain birch (Betula pubescens ssp. czerepanovii) trees were provided with a 13CO2 pulse using portable field equipment, and leaf samples were collected from neighbouring con-specific trees and hetero-specific understorey shrubs on days 1–10 and 377 post-crown labelling. We found effective and long-term enrichment of foliage in labelled trees, but no evidence of the 13C-signal in con- or hetero-specific neighbouring trees or woody shrubs. This method is promising and provides a valuable tool to isolate the role of canopy tree species in ecosystems with dense understorey cover.Output Status: Forthcoming/Available Onlin

Resistance of subarctic soil fungal and invertebrate communities to disruption of below-ground carbon supply

The supply of recent photosynthate from plants to soils is thought to be a critical mechanism regulating the activity and diversity of soil biota. In the Arctic, large-scale vegetation transitions are underway in response to warming, and there is an urgent need to understand how these changes affect soil biodiversity and function. We investigated how abundance and diversity of soil fungi and invertebrates responded to a reduction in fresh below-ground photosynthate supply in treeline birch and willow, achieved using stem girdling. We hypothesised that birch forest would support greater abundance of ectomycorrhizal (ECM) fungal species and fauna than willow shrubs, and that girdling would result in a rapid switch from ECM fungi to saprotrophs as canopy supply of C was cut, with a concomitant decline in soil fauna. Birch forest had greater fungal and faunal abundance with a large contribution of root-associated ascomycetes (ericoid mycorrhizal fungi and root endophytes) compared to willow shrub plots, which had a higher proportion of saprotrophs and, contrary to our expectations, ECM fungi. Broad-scale soil fungal and faunal functional group composition was not significantly changed by girdling, even in the third year of treatment. Within the ECM community, there were some changes, with genera that are believed to be particularly C-demanding declining in girdled plots. However, it was notable how most ECM fungi remained present after 3 years of isolation of the below-ground compartment from contemporary photosynthate supply. Synthesis. In a treeline/tundra ecosystem, distinct soil communities existed in contrasting vegetation patches within the landscape, but the structure of these communities was resistant to canopy disturbance and concomitant reduction of autotrophic C inputs

Rhizosphere allocation by canopy-forming species dominates soil CO2 efflux in a subarctic landscape

In arctic ecosystems, climate change has increased plant productivity. As arctic carbon (C) stocks are predominantly located below ground, the effects of greater plant productivity on soil C storage will significantly determine the net sink/source potential of these ecosystems, but vegetation controls on soil CO2 efflux remain poorly resolved. To identify the role of canopy‐forming species in below‐ground C dynamics, we conducted a girdling experiment with plots distributed across 1 km2 of treeline birch (Betula pubescens) forest and willow (Salix lapponum) patches in northern Sweden and quantified the contribution of canopy vegetation to soil CO2 fluxes and below‐ground productivity. Girdling birches reduced total soil CO2 efflux in the peak growing season by 53% ‐double the expected amount, given that trees contribute only half of the total leaf area in the forest. Root and mycorrhizal mycelial production also decreased substantially. At peak season, willow shrubs contributed 38% to soil CO2 efflux in their patches. Our findings indicate that C, recently fixed by trees and tall shrubs, makes a substantial contribution to soil respiration. It is critically important that these processes are taken into consideration in the context of a greening arctic since productivity and ecosystem C sequestration are not synonymous

Shrub expansion in the Arctic may induce large-scale carbon losses due to changes in plant-soil interactions

Background Tall deciduous shrubs are increasing in range, size and cover across much of the Arctic, a process commonly assumed to increase carbon (C) storage. Major advances in remote sensing have increased our ability to monitor changes aboveground, improving quantification and understanding of arctic greening. However, the vast majority of C in the Arctic is stored in soils, where changes are more uncertain. Scope We present pilot data to argue that shrub expansion will cause changes in rhizosphere processes, including the development of new mycorrhizal associations that have the potential to promote soil C losses that substantially exceed C gains in plant biomass. However, current observations are limited in their spatial extent, and mechanistic understanding is still developing. Extending measurements across different regions and tundra types would greatly increase our ability to predict the biogeochemical consequences of arctic vegetation change, and we present a simple method that would allow such data to be collected. Conclusions Shrub expansion in the Arctic could promote substantial soil C losses that are unlikely to be offset by increases in plant biomass. However, confidence in this prediction is limited by a lack of information on how soil C stocks vary between contrasting Arctic vegetation communities; this needs to be addressed urgently