Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis

Recently, diabetic gastroparesis(DGP) has received much attention as its prevalence is increasing in a dramatic fashion and management of patients with DGP represents a challenge in the clinical practice due to the limited therapeutic options. DGP highlights an interrelationship between the gastric emptying and pancreatic secretory function that regulate a wide range of digestive and metabolic functions, respectively. It well documented that both gastric emptying and pancreatic secretion are under delicate control by multiple neurohormonal mechanisms including extrinsic parasympathetic pathways and gastrointestinal(GI) hormones. Interestingly, the latter released in response to various determinants that related to the rate and quality of gastric emptying. Others and we have provided strong evidence that the central autonomic nuclei send a dual output(excitatory and inhibitory) to the stomach and the pancreas in response to a variety of hormonal signals from the abdominal viscera. Most of these hormones released upon gastric emptying to provide feedback, and control this process and simultaneously regulate pancreatic secretion and postprandial glycemia. These findings emphasize an important link between gastric emptying and pancreatic secretion and its role in maintaining homeostatic processes within the GI tract. The present review deals with the neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function that implicated in DGP and this provides new insights in our understanding of the pathophysiology of DGP. This also enhances the process of identifying potential therapeutic targets to treat DGP and limit the complications of current management practices.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Peripheral reflex feedbacks in chronic heart failure:Is it time for a direct treatment?

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure(HF),no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed,the neurohormonal model,has the great virtue of highlighting the role of the heart as an endocrine organ,as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However,while survival in clinical trials based on neurohormonal antagonist drugs has improved,HF currently remains a lethal condition. At the borders of the neurohormonal model of HF,a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences,from both animal studies and humans reports,that the deregulation of baro-,ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart,thus fundamentally contributing to the evolution of the disease. Hence,on top of guidelinerecommended medical therapy,mainly based on neurohormonal antagonisms,all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.

Transcriptional regulation analysis reveals the complexity of metamorphosis in the Pacific oyster(Crassostrea gigas)

Many marine invertebrate phyla are characterized by indirect development.These animals transit from planktonic larvae to benthic spats via settlement and metamorphosis,which contributes to their adaption to the marine environment.Studying the biological process of metamorphosis is,thus,key to understanding the origin and evolution of indirect development.Although numerous studies have been conducted on the relationship between metamorphosis and the marine environment,microorganisms,and neurohormones,little is known about gene regulation network(GRN)dynamics during metamorphosis.Metamorphosis-competent pediveligers of the Pacific oyster Crassostrea gigas were assayed in this study.By assaying gene expression patterns and open chromatin region changes of different samples of larvae and spats,the dynamics of molecular regulation during metamorphosis were examined.The results indicated significantly different gene regulation networks before,during and post-metamorphosis.Genes encoding membrane-integrated receptors and those related to the remodeling of the nervous system were upregulated before the initiation of metamorphosis.Massive biogenesis,e.g.,of various enzymes and structural proteins,occurred during metamorphosis as inferred from the comprehensive upregulation of the protein synthesis system post epinephrine stimulation.Hierarchical downstream gene networks were then stimulated.Some transcription factors,including homeobox,basic helix–loop–helix and nuclear receptors,showed different temporal response patterns,suggesting a complex GRN during the transition stage.Nuclear receptors,as well as their retinoid X receptor partner,may participate in the GRN controlling oyster metamorphosis,indicating an ancient role of the nuclear receptor regulation system in animal metamorphosis.

A miniaturized assay to quantify effects of chemicals or physical stimuli upon locust activity

Solitary and gregarious locusts differ in many traits, such as body color, morphometrics and behavior. With respect to behavior, solitary animals shun each other, while gregarious animals seek each other＇s company, hence their crowding behavior. General activity, depending on the temperature, occurs throughout the day but is much lower in solitary locusts. Solitary locusts occasionally fly by night while gregarious locusts fly regularly during daytime （swarming）. In search of new assays to identify substances that control or modify aspects of （phase） behavior, we designed a simple activity assay, meant to complement existing behavioral measurement tools. The general activity is reflected in the number of wall hits, that is, the number of contacts between the locust and the vertical walls of a small arena. Using this single parameter we were able to quantify differences in total activity of both nymphs and adults of isolation-reared （solitary）, regrouped- and crowdreared （gregarious） locusts under different conditions. Furthermore, we demonstrate that there are inter- and intra-phase dependent differences in activities of 5th instar nymphs afar injections of the three different adipokinetic hormones.

Short neuropeptide F in integrated insect physiology

The short neuropeptide F(sNPF)family of peptides is a multifunctional group of neurohormones involved in the regulation of various physiological processes in insects.They have been found in a broad spectrum of species,but the number of isoforms in the precursor molecule varies from one to four.The receptor for sNPF(sNPFR),which belongs to the G protein-coupled receptor family,has been characterized in various insect orders and was shown to be an ortholog of the mammalian prolactin-releasing peptide receptor(PrPR).The sNPF signaling pathway interacts with other neurohormones such as insulin-like peptides,SIFamide,and pigment-dispersing factors(PDFs)to regulate various processes.The main physiological function of sNPF seems to be involved in the regulation of feeding,but the observed effects are species-specific.sNPF is also connected with the regulation of foraging behavior and the olfactory system.The influence of sNPF on feeding and thus energy metabolism may also indirectly affect other vital processes,such as reproduction and development.In addition,these neurohormones are involved in the regulation of locomotor activity and circadian rhythm in insects.This review summarizes the current state of knowledge about the sNPF system in insects.