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Abstract The maintenance of glucose homeostasis is obligatory for health and survival. It relies on peripheral glucose sensing and signalling between the brain and peripheral organs via hormonal and neural responses that restore euglycaemia. Failure of these mechanisms causes hyperglycaemia or diabetes. Current anti‐diabetic medications control blood glucose but many patients remain with hyperglycemic condition. Diabetes is often associated with hypertension; the latter is more difficult to control in hyperglycaemic conditions. We ask whether a better understanding of the regulatory mechanisms of glucose control could improve treatment of both diabetes and hypertension when they co‐exist. With the involvement of the carotid body (CB) in glucose sensing, metabolic regulation and control of sympathetic nerve activity, we consider the CB as a potential treatment target for both diabetes and hypertension. We provide an update on the role of the CB in glucose sensing and glucose homeostasis. Physiologically, hypoglycaemia stimulates the release of hormones such as glucagon and adrenaline, which mobilize or synthesize glucose; however, these counter‐regulatory responses were markedly attenuated after denervation of the CBs in animals. Also, CB denervation prevents and reverses insulin resistance and glucose intolerance. We discuss the CB as a metabolic regulator (not just a sensor of blood gases) and consider recent evidence of novel ‘metabolic’ receptors within the CB and putative signalling peptides that may control glucose homeostasis via modulation of the sympathetic nervous system. The evidence presented may inform future clinical strategies in the treatment of patients with both diabetes and hypertension, which may include the CB.

The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.

The carotid body is the primary peripheral chemoreceptor in the body, and critical for respiration and cardiovascular adjustments during hypoxia. Yet considerable evidence now implicates the carotid body as a multimodal sensor, mediating the chemoreflexes of a wide range of physiological responses, including pH, temperature, and acidosis as well as hormonal, glucose and immune regulation. How does the carotid body detect and initiate appropriate physiological responses for these diverse stimuli? The answer to this may lie in the structure of the carotid body itself. We suggest that at an organ-level the carotid body is comparable to a miniature brain with compartmentalized discrete regions of clustered glomus cells defined by their neurotransmitter expression and receptor profiles, and with connectivity to defined reflex arcs that play a key role in initiating distinct physiological responses, similar in many ways to a switchboard that connects specific inputs to selective outputs. Similarly, within the central nervous system, specific physiological outcomes are co-ordinated, through signaling via distinct neuronal connectivity. As with the brain, we propose that highly organized cellular connectivity is critical for mediating co-ordinated outputs from the carotid body to a given stimulus. Moreover, it appears that the rudimentary components for synaptic plasticity, and learning and memory are conserved in the carotid body including the presence of glutamate and GABAergic systems, where evidence pinpoints that pathophysiology of common diseases of the carotid body may be linked to deviations in these processes. Several decades of research have contributed to our understanding of the central nervous system in health and disease, and we discuss that understanding the key processes involved in neuronal dysfunction and synaptic activity may be translated to the carotid body, offering new insights and avenues for therapeutic innovation.

Summary: Desert animals have evolved systems that enable them to thrive under dry conditions. Focusing on the kidney, we have investigated the transcriptomic adaptations that enable a desert rodent, the Lesser Egyptian Jerboa (Jaculus jaculus), to withstand water deprivation and opportunistic rehydration. Analysis of the whole kidney transcriptome showed many differentially expressed genes in the Jerboa kidney, 6.4% of genes following dehydration and an even greater number (36.2%) following rehydration compared to control. Genes correlated with the rehydration condition included many ribosomal protein coding genes suggesting a concerted effort to accelerate protein synthesis when water is made available. We identify an increase in TGF-beta signaling antagonists in dehydration (e.g., GREM2). We also describe expression of multiple aquaporin and solute carrier transporters mapped to specific nephron segments. The desert adapted renal transcriptome presented here is a valuable resource to expand our understanding of osmoregulation beyond that derived from model organisms.

Comparative transcriptomic analyses between dromedary camels and rats provide insight into water homeostasis gene responses in animals under water stress conditions.

Fernando Alvira-Iraizoz and Benjamin T. Gillard et al. comprehensively catalogue the kidney transcriptome and proteome of dromedary camels in response to chronic dehydration stress and subsequent acute rehydration. Their results suggest that the suppression of the cholesterol biosynthesis may facilitate water retention in the dromedary camel kidney, providing further insight into how these animals survive in arid conditions.

The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.

Ultradian glucocorticoid rhythms are highly conserved across mammalian species, however, their functional significance is not yet fully understood. Here we demonstrate that pulsatile corticosterone replacement in adrenalectomised rats induces a dynamic pattern of glucocorticoid receptor (GR) binding at ~3,000 genomic sites in liver at the pulse peak, subsequently not found during the pulse nadir. In contrast, constant corticosterone replacement induced prolonged binding at the majority of these sites. Additionally, each pattern further induced markedly different transcriptional responses. During pulsatile treatment, intragenic occupancy by active RNA polymerase II exhibited pulsatile dynamics with transient changes in enrichment, either decreased or increased depending on the gene, which mostly returned to baseline during the inter-pulse interval. In contrast, constant corticosterone exposure induced prolonged effects on RNA polymerase II occupancy at the majority of gene targets, thus acting as a sustained regulatory signal for both transactivation and repression of glucocorticoid target genes. The nett effect of these differences were consequently seen in the liver transcriptome as RNA-seq analysis indicated that despite the same overall amount of corticosterone infused, twice the number of transcripts were regulated by constant corticosterone infusion, when compared to pulsatile. Target genes that were found to be differentially regulated in a pattern-dependent manner were enriched in functional pathways including carbohydrate, cholesterol, glucose and fat metabolism as well as inflammation, suggesting a functional role for dysregulated glucocorticoid rhythms in the development of metabolic dysfunction.