Alarin potentiates ongoing epileptiform activity in rat brain slices: an in vitro electrophysiological study.

Alarin is a newly discovered neuropeptide that belongs to the galanin peptide family with a wide range of bioactivity in the nervous system. Its function in the brain's autonomic areas has been studied, and it has been reported that alarin is involved in the regulation of excitability in hypothalamic neurons. Its role in the regulation of excitability in the hippocampus, however, is unknown. In this study, we investigated if alarin induced any synchronous discharges or epileptiform activity, and if it had any effect on already initiated epileptiform discharges. We used thick acute horizontal hippocampal slices obtained from 30­ to 35­day­old rats. Extracellular field potential recordings were evaluated in the CA1 region of the hippocampus. Our data demonstrated that, alarin application did not result in any epileptiform activity or abnormal discharges. 4­aminopyridine was applied to induce epileptiform activity in the slices. We found that alarin increased the frequency of interictal­like events and the mean power of local field potentials in the CA1 region of the hippocampus, which was induced by 4­aminopyridine. These results demonstrated for the first time that alarin has a modulatory effect on synchronized neuronal discharges and showed the contribution of the neuropeptide alarin to epilepsy­like conditions.

Effect of Intracerebroventricular Administration of Galanin-Like Peptide on Hepatokines in C57BL/6 J Mice.

Galanin-like peptide (GALP) is a neuropeptide that was first isolated and identified from the porcine hypothalamus. Studies have described an anti-obesity effect of GALP. We previously found that intracerebroventricular administration of GALP in mice resulted in an increase in respiratory exchange rate 12 to 16 h later. GALP may also affect glucose metabolism, but the detailed mechanism has not been elucidated. In this study, we investigated the effects of GALP on glucose and lipid metabolism in the liver. Nine-week-old male C57BL / 6 J mice were administered a single intracerebroventricular dose of saline or GALP and dissected 16 h later. There were no significant between-group differences in body weight and blood glucose levels. With regard to gene and protein expression, G6Pase associated with hepatic gluconeogenesis was significantly reduced in the GALP group. In addition, the hepatokines selenoprotein P and fetuin-A, which induce insulin resistance in the liver, were significantly decreased in the GALP group. These results suggest that intracerebroventricular administration of GALP decreases the expression of key hepatokines, thereby enhancing glucose metabolism.

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide).

The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (Fmo3), metallothionein 1 and 2 (Mt1 and Mt2, respectively), and the Aldh1a3, Defa3, and Defa20 genes. Analysis using the DAVID tool showed that intranasal GALP enhanced gene expression related to fatty acid elongation and unsaturated fatty acid synthesis and downregulated gene expression related to lipid and cholesterol synthesis, fat absorption, bile uptake, and excretion. Metabolite analysis revealed increased levels of coenzyme Q10 and oleoylethanolamide in the liver tissue, increased levels of deoxycholic acid (DCA) and taurocholic acid (TCA) in the bile acids, increased levels of taurochenodeoxycholic acid (TCDCA), and decreased levels of ursodeoxycholic acid (UDCA). In conclusion, intranasal GALP administration alleviated weight gain in obese mice fed an HFD via mechanisms involving antioxidant, anti-inflammatory, and fatty acid metabolism effects and genetic alterations. The gene expression data are publicly available at NCBI GSE243376.

Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide (GALP) signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

Galanin-like peptide and its correlation with androgen levels in patients with polycystic ovary syndrome.

INTRODUCTION: We aimed to investigate serum galanin-like peptide (GALP) levels and their correlation with hormonal and metabolic parameters in patients with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study included 48 women (age range, 18-44 years) with a diagnosis of PCOS, and a control group that included 40 healthy females (age range, 18-46 years). Waist circumference, body mass index (BMI), and Ferriman-Gallwey score were evaluated and plasma glucose, lipid profile, oestradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulphate (DHEA-S), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D (25(OH)D), fibrinogen, d-dimer, C-reactive protein (CRP), and GALP levels were measured in all study subjects. RESULTS: Waist circumference (p = 0.044) and Ferriman-Gallwey score (p = 0.002) were significantly higher in patients with PCOS compared to the control group. Among the metabolic and hormonal parameters studied, only total testosterone was significantly higher in patients with PCOS (p = 0.002). Also, the serum 25(OH)D level was significantly lower in the PCOS group (p = 0.001). CRP, fibrinogen, and D-dimer levels were all similar between the 2 groups. Serum GALP level was significantly higher in PCOS patients (p = 0.001). GALP was negatively correlated with 25(OH)D (r = -0.401, p = 0.002) and positively correlated with total testosterone values (r = 0.265, p = 0.024). Multiple regression analysis revealed that both total testosterone and 25(OH)D significantly contributed to GALP levels. CONCLUSIONS: Our study is the first in the literature to evaluate serum GALP levels in patients with PCOS. Increased GALP levels in PCOS and its association with total testosterone levels might show that GALP can act as an intermediary in increased GnRH-mediated LH release, which is one of the underlying pathogenetic mechanism of PCOS.

The evolving roles of alarin in physiological and disease conditions, and its future potential clinical implications.

Alarin is a member of the galanin family of neuropeptides that is widely expressed in the central nervous system and peripheral tissues in humans and rodents. It was initially isolated fifteen years ago in ganglionic cells of human neuroblastoma. Subsequently, it was demonstrated to be broadly distributed in the blood vessels, skin, eyes, peripheral and central nervous systems, thymus, gastrointestinal tract, and endocrine organs of different species. Alarin is a 25 amino acid neuropeptide derived from the alternative splicing of the GALP gene, missing exon 3. It is found to be involved in several physiological functions that include feeding behavior, energy homeostasis, glucose homeostasis, body temperature, and reproduction. It has also vasoactive, anti-inflammatory, anti-edema, and antimicrobial activities. However, the physiological effects of alarin have not been fully elucidated and the receptors that mediate these effects are not currently known. Unearthing the novel biological effects of alarin and its unidentified receptors will therefore be a task in future biomedical research. In addition, alarin is involved in various disease conditions, such as metabolic syndrome, obesity, insulin resistance, type 2 diabetes, diabetic retinopathy, hypertension, cardiac fibrosis, polycystic ovarian syndrome, and depression. Thus, alarin may serve as a promising tool for future pharmacological treatment and diagnosis. But further research is awaited to confirm whether alarin has a protective or pathological role in these diseases. This article provides a comprehensive review on the evolving implications of alarin in a variety of physiological and disease conditions, and its future perspectives.

Plasma and aqueous levels of alarin and adipsin in patients with and without diabetic retinopathy.

BACKROUND: Diabetic retinopathy is a disease seen with microvascular complications as a result of hyperglycemia and insulin resistance. Alarin and Adipsin are molecules with a role in energy and glucose metabolism. The aim of this study was to determine plasma and aqueous levels of Alarin and Adipsin in patients with and without diabetic retinopathy to evaluate their potential roles in diabetic retinopathy. METHODS: The study included one eye from each of 20 cataract patients without diabetes (C), 20 cataract patients with diabetes and without diabetic retinopathy (DM + C), and 20 cataract patients with diabetes and diabetic retinopathy (DR + C). Plasma and aqueous humour samples were taken from all patients during the cataract operation. Alarin and Adipsin levels were examined with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Both plasma and aqueous Alarin levels were significantly higher in the patients with diabetic retinopathy than in the control group (p < 0.001, p = 0.006). Adipsin levels were found to be significantly higher in plasma in the control group than in the DR + C group and significantly higher in aqueous in the DR + C group than in the control group (p < 0.001, p < 0.001). CONCLUSION: These findings suggest that Alarin and Adipsin may play important role in diabetic retinopathy.

Effects of Galp and alarin peptides on HPA axis gene expression and adrenal function: In vivo experiments.

BACKGROUND: Many experimental data indicate interactions between peptides involved in the control of food intake, energy homeostasis and adrenocortical hormone release. Glucocorticoids stimulate or inhibit the secretion of orexigenic and anorexigenic peptides, which in turn are involved in the regulation of adrenal growth, structure and function. Galanin-like peptide (Galp) and alarin (Ala) are involved in the regulation of food intake. Galp and Ala mRNAs have already been shown to be present in the arcuate nucleus (ARC) of the hypothalamus in both rats and mice. OBJECTIVES: To investigate the expression of Ala, Galp and their receptors in the hypothalamus and pituitary and adrenal glands of the rat hypothalamic-pituitary-adrenal (HPA) axis after intraperitoneal administration of peptides in vivo. MATERIAL AND METHODS: Experimental in vivo models were used: acute and long-term exposure to peptides. RESULTS: The expression of Galp, Ala, their receptors, and steroidogenesis enzymes was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Statistically significant expression changes were found in the hypothalamus and pituitary after 1-hour exposure to the peptides, such as a decrease in corticotropin-releasing hormone (CRH) expression after Ala, Galp and adrenocorticotropic hormone (ACTH) administration, and a decrease in the expression of receptors for galanin (Gal) (Galr1 and Galr2). In the pituitary, there was a statistically significant increase in the expression of Ala, Galr1, Galr2, and Galr3 receptors 1 h after Galp administration. In the adrenal glands, only a statistically significant decrease in Galr2 expression was observed after 1 h of Ala 0.5 administration. The mRNA expression of steroidogenesis enzymes also changed: for example, the expression of cholesterol desmolase increased 24 h after Ala peptide administration. CONCLUSIONS: The results indicate that the peptides tested under in vivo conditions can alter the expression of the peptides tested, as well as of Galp, Ala and Gal receptors and steroidogenesis enzymes - Cyp11a1 (cholesterol desmolase), Cyp11b1 (11ß-hydroxylase) and Cyp11b2 (aldosterone synthase).

Alarin: A new predictive marker in infertile women with polycystic ovary syndrome: A case-control study.

AIM: There is scant evidence concerning the relationship of alarin concentrations for polycystic ovary syndrome (PCOS) status in the existing literature. Therefore, we aimed to reveal the relationship about predictive value of serum alarin concentrations for PCOS risk in infertile women. METHODS: This prospective case-control study included a total of 151 infertile women who met eligibility criteria of the study. Infertile women diagnosed with PCOS formed the study group (n = 80). Women with diagnoses of unexplained infertility constituted the control group (n = 71). The biochemical analyses of serum concentrations of lipid profiles, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH) and alarin were performed. RESULTS: There were no differences for the study parameters, including age, body mass index, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total triglyceride, E2, and FSH levels in either group. Serum LH, AMH, alarin concentrations, and antral follicle counts had higher values in the PCOS group compared with the controls. Correlation analysis revealed that serum alarin levels were significantly positively correlated with LH and AMH levels, only in the PCOS group. Multivariate binary logistic regression analysis demonstrated that infertile women with high alarin concentrations were significantly more likely to develop PCOS (OR = 1.77, 95% CI = 0.095-0.332, p < 0.001). CONCLUSION: Higher serum concentrations of alarin and a positive correlation with serum LH levels were found in infertile women with PCOS. This evidence supported that high alarin concentrations might play a role in the development of PCOS.

Alarin moderated myocardial hypertrophy via inhibiting cyclic adenosine monophosphate/protein kinase A signaling pathway to attenuate autophagy.

Alarin could alleviate myocardial infarction-induced heart failure. The present study was to explore whether alarin could alleviate myocardial hypertrophy via inhibiting cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway to attenuate autophagy. Myocardial hypertrophy was induced by angiotensin (Ang) II infusion in vivo in mice and by Ang II treatment of neonatal rat cardiomyocytes (NRCMs) in vitro. The Ang II-induced hypertrophy and fibrosis of the heart were alleviated after alarin administration in mice. The increased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (ß-MHC), and the decreased alpha-myosin heavy chain (α-MHC) induced by Ang II were reversed by alarin treatment in NRCMs. Alarin inhibited the increases of cAMP and PKA in NRCMs. Treatment with cAMP or overexpression of PKA blocked the attenuating effects of alarin on Ang II-induced hypertrophy in NRCMs. Alarin reduced the Ang II-induced increases of LC3, Beclin 1, autophagy-related gene (Atg)3 and Atg5 in NRCMs. The overexpression of cAMP and PKA reversed the alleviating effects of alarin on the increased autophagy induced by Ang II in NRCMs. These results indicated that alarin could moderate cardiac remodeling. Alarin improved myocardial hypertrophy via inhibiting the cAMP/PKA signaling pathway to attenuate autophagy.

The circulating alarin level was elevated in infertile women with poor ovarian reserve.

OBJECTIVE: We aimed to reveal the association of serum alarin level with POR status of the infertile women in the present study. METHODS: The eligibility criteria for this prospective cross-sectional study included a total of 92 infertile women attending the Hitit University Hospital, and all participant women were categorized into two main groups of ovarian reserve: (i) Poor ovarian reserve (POR) group (n = 40) based on ESHRE consensus and (ii) Control group (NOR) (n = 52). RESULTS: The mean adjusted-ages and BMI values of the NOR and POR groups were statistically comparable (p = .057 and p = .600, respectively). The mean E2, FSH, and LH levels were elevated in the POR group (p < .001, for all). The mean AFC and AMH concentration were significantly reduced in the POR group (p < .001, for both). In addition, there was a significant increase in the serum alarin level in the POR group (p < .001). Pearson's analysis revealed that the mean BMI value of the POR group had a weak and negative correlation (r = 0.318, p = .046). Also, there was no correlation between serum alarin with E2 and FSH levels in both study groups. A weak and positive correlation was found between serum alarin and LH concentration only in the POR group (r = 0.318, p = .045). The mean AMH and AFC values were not significantly correlated with serum alarin levels. CONCLUSION: The circulating alarin level was significantly elevated in infertile women with POR patterns. In addition, the alarin level was significantly correlated with the serum LH concentration in the POR pattern.

Alarin alleviated cardiac fibrosis via attenuating oxidative stress in heart failure rats.

The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague-Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dtmax) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-ß were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-ß expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.

Superoxide anions modulate the effects of alarin in the paraventricular nucleus on sympathetic activity and blood pressure in spontaneously hypertensive rats.

Neuropeptides are involved in the regulation of the sympathetic activity and blood pressure in the paraventricular nucleus of the hypothalamus (PVN). The present study was designed to determine how alarin modulates the renal sympathetic nerve activity (RSNA), arterial blood pressure and mean arterial pressure (MAP) in the PVN, and whether superoxide anions regulate the effects of alarin in the PVN of spontaneously hypertensive rats (SHRs). Acute experiment was carried out with male Wistar-Kyoto rats (WKY) and SHRs under anesthesia. RSNA, systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were measured. Alarin microinjection into the PVN increased RSNA (7.8 ± 1.8 vs. 14.8 ± 2.3%), SBP (5.9 ± 1.4 vs. 12.1 ± 1.6 mmHg), DBP (5.1 ± 0.8 vs. 10.0 ± 1.1 mmHg), and MAP (5.4 ± 1.2 vs. 10.7 ± 1.3 mmHg) in WKY rats and SHRs,. Alarin antagonist ala6-25 Cys decreased RSNA, SBP, DBP, and MAP in SHRs, and inhibited the effects of alarin. The alarin level was increased in the PVN of SHR compared to WKY rats. (29.7 ± 4.9 vs. 14.6 ± 2.4 pg/mg protein). PVN microinjection of superoxide anion scavengers tempol and tiron, or NAD(P)H oxidase inhibitor apocynin, decreased RSNA, SBP, DBP, and MAP in SHRs, and inhibited the effects of alarin, but the superoxide dismutase inhibitor diethyldithiocarbamic acid potentiated the effects of alarin. Superoxide anions and NAD(P)H oxidase activity levels in the PVN were increased by alarin, but decreased by alarin antagonist ala6-25 Cys. The alarin-induced increases in superoxide anions and NAD(P)H oxidase activity levels were abolished by pre-treatment with ala6-25 Cys. The results suggest that alarin in the PVN increases sympathetic outflow and blood pressure. The enhanced activity of endogenous alarin in the PVN contributes to sympathetic activation in hypertension, and the superoxide anion is involved in these alarin-mediated processes in the PVN.

Galanin peptide family regulation of glucose metabolism.

Recent preclinical and clinical studies have indicated that the galanin peptide family may regulate glucose metabolism and alleviate insulin resistance, which diminishes the probability of type 2 diabetes mellitus. The galanin was discovered in 1983 as a gut-derived peptide hormone. Subsequently, galanin peptide family was found to exert a series of metabolic effects, including the regulation of gut motility, body weight and glucose metabolism. The galanin peptide family in modulating glucose metabolism received recently increasing recognition because pharmacological activiation of galanin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes mellitus. To date, however, few papers have summarized the role of the galanin peptide family in modulating glucose metabolism and insulin resistance. In this review we summarize the metabolic effect of galanin peptide family and highlight its glucoregulatory action and discuss the pharmacological value of galanin pathway activiation for the treatment of glucose intolerance and type 2 diabetes mellitus.

[Level of circulating Alarin in obese children and its association with insulin resistance].

OBJECTIVE: To study the level of circulating Alarin in obese children and its association with various metabolic parameters. METHODS: A total of 86 obese children with a body mass index (BMI) above the 95th percentile were enrolled as the obesity group, and 82 healthy children, matched for age and sex, with a BMI below the 85th percentile were enrolled as the healthy control group. According to the presence or absence of insulin resistance (IR), the obesity group was further divided into an IR group with 27 children and a non-IR group with 59 children. Related anthropometric parameters, including body height, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were measured, and BMI was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), fasting insulin (FINS), and fasting blood glucose (FBG) were measured. The area under the receiver operating characteristic curve (AUC) for glucose and insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and whole-body insulin sensitivity index (WBISI) were calculated. ELISA was used to measure the level of circulating Alarin. RESULTS: The obesity group had a significantly higher level of circulating Alarin than the healthy control group (P<0.01). The IR group had a significantly higher level of circulating Alarin than the non-IR group (P<0.01). Circulating Alarin was positively correlated with BMI, TG, FBG, AUC-glucose, AUC-FINS, and HOMA-IR (P<0.05) and was negatively correlated with WBISI (P<0.05). The circulating Alarin level had a linear regression relationship with BMI, FBG, and HOMA-IR, among which HOMA-IR had the greatest influence on the circulating Alarin level (P<0.05). CONCLUSIONS: There is a significant increase in the circulating Alarin level in obese children, which may be associated with the development of obesity and IR.

Circulating alarin concentrations are high in patients with type 2 diabetes and increased by glucagon-like peptide-1 receptor agonist treatment: An Consort-compliant study.

CONTEXT: Alarin has been reported to be relative to food intake and an increase in body weight. However, to date, no report has demonstrated the relationship between circulating alarin and diabetes in humans. OBJECTIVE: The objective of this study is to gain insight into the possible role of alarin in humans. DESIGN AND METHODS: 164 patients with newly diagnosed type 2 diabetes mellitus (nT2DM), 112 IGT and 134 healthy subjects were recruited for this study. In an interventional study, 29 nT2DM patients were treated by a weekly GLP-1RA for 6 months. Plasma alarin concentrations were measured by ELISA. RESULTS: Circulating alarin concentrations were significantly higher in both IGT and nT2DM subjects than in healthy individuals (0.40 ±â€Š0.14 and 0.54 ±â€Š0.24 vs 0.37 ±â€Š0.10 µg/L, P < .05 or P < .01), whereas in T2DM patients, circulating alarin levels were higher than in IGT subjects. Circulating alarin positively correlated with FBG, HbA1c, HOMA-IR, AUCglucose and TNFα (P < .05 or P < .01). Multivariate logistic regression revealed that circulating alarin levels were correlated with IGT and T2DM. GLP-1RA treatment for 6 months increased circulating alarin levels in T2DM patients (from 0.34 ±â€Š0.10 for baseline, to 0.39 ±â€Š0.14 for 12 weeks, and finally to 0.38 ±â€Š0.15 µg/L for 24 weeks; vs. pre-treatment P < .05). CONCLUSIONS: These data suggest that alarin might be involved in the pathogenesis of T2DM in humans. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OCS-13003185 (18/03/2013 ).

Expression profile of Galp, alarin and their receptors in rat adrenal gland.

BACKGROUND: Galanin-like peptide (Galp) and alarin (Ala) are 2 new members of the galanin peptide family. Galanin (Gal), the "parental" peptide of the entire family, is known to regulate numerous physiological processes, including energy and osmotic homeostasis, reproduction, food intake, and secretion of adrenocortical hormones. Galp and Ala are known to regulate food intake. In the rat, Galp mRNA has been found in the brain, exclusively in the hypothalamic arcuate nucleus (ARC) and median eminence, which are involved in the regulation of energy homeostasis. Alarin-like immunoreactivity is present in the locus coeruleus (LC) and the ARC of rats and mice. OBJECTIVES: The aim of the study was to investigate the expression of Ala, Galp and their receptors in the organs of the hypothalamo-pituitary-adrenal (HPA) axis of the rat. MATERIAL AND METHODS: The expression of the examined genes was measured in different models of adrenal growth of the rat in vivo (postnatal ontogenesis, compensatory adrenal growth, adrenocortical regeneration, adrenocorticotropic hormone (ACTH) administration). The expression was evaluated using the Affymetrix® microarray system or quantitative polymerase chain reaction (qPCR). RESULTS: The expression of Ala gene was observed in each organ of the HPA axis (the hypothalamus, hypophysis and adrenal gland). The elevated level of expression of this gene was observed in the pituitary of 2-day rats, while very low levels of Ala mRNA were observed in the adrenals. Galp mRNA expression was observed only in the hypothalamus and the hypophysis during postnatal ontogenesis. The expression of Gal receptors was demonstrated in the hypothalamus, the hypophysis and the adrenal gland. In different compartments of the adrenal glands of adult, intact male and female rats, the expression of Ala, Galp and galanin receptor 1 (Galr1) genes was negligible, but the expression of galanin receptor 2 (Galr2), galanin receptor 3 (Galr3) and neurotrophic receptor tyrosine kinase 2 (Ntrk2) genes was noticeable. CONCLUSIONS: The examined genes showed different expression levels within the studied HPA axis; some of them were neither expressed in the hypothalamus or the pituitary gland, nor in the adrenal gland.

Alarin in different human intestinal epithelial cell types.

Alarin (AL), a new member of the galanin family, has been localized in various CNS regions, mainly in rodents. Among other effects, it modulates food intake. Therefore, we analyzed the immunohistochemical distribution pattern of AL in human intestinal epithelia. Cryosections of 12 human bowel samples were immunohistochemically double-stained for AL and α-defensin 5 (αD; first set). Two further sets of sections were quadruple-stained either (second set) for AL, chromogranin (CG), synaptophysin (SY), and somatostatin (SO) or (third set) for AL, CG, Peptide Y (PY), and 5-hydroxytryptamine (5-HT). Slides were digitized and quantitative analysis of co-localization rates was undertaken. Small bowel: most of AL-positive cells (56%) were αD-positive Paneth cells located within the base of the crypts (first set). In the second set, about 27% of AL-labeled cells were co-reactive for SY and CG, likely representing entero-endocrine cells. In the third set, the largest subpopulation of AL-positive cells was not co-reactive for other markers applied (89%); most of them were likely Paneth cells. Large bowel: co-localization of AL with αD was not detected (first set). In the second set, AL was frequently co-localized with the other three markers applied (68%). In the third set, AL was frequently co-localized with 5-HT and CG (31%) as well as with PY and 5-HT (22%). Due to its presence in various enteroendocrine as well as Paneth cells, AL may be involved in different physiological and pathological processes.

Level of circulating Alarin in obese children and its association with insulin resistance / 中国当代儿科杂志

OBJECTIVE@#To study the level of circulating Alarin in obese children and its association with various metabolic parameters.@*METHODS@#A total of 86 obese children with a body mass index (BMI) above the 95th percentile were enrolled as the obesity group, and 82 healthy children, matched for age and sex, with a BMI below the 85th percentile were enrolled as the healthy control group. According to the presence or absence of insulin resistance (IR), the obesity group was further divided into an IR group with 27 children and a non-IR group with 59 children. Related anthropometric parameters, including body height, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were measured, and BMI was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), fasting insulin (FINS), and fasting blood glucose (FBG) were measured. The area under the receiver operating characteristic curve (AUC) for glucose and insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and whole-body insulin sensitivity index (WBISI) were calculated. ELISA was used to measure the level of circulating Alarin.@*RESULTS@#The obesity group had a significantly higher level of circulating Alarin than the healthy control group (P<0.01). The IR group had a significantly higher level of circulating Alarin than the non-IR group (P<0.01). Circulating Alarin was positively correlated with BMI, TG, FBG, AUC-glucose, AUC-FINS, and HOMA-IR (P<0.05) and was negatively correlated with WBISI (P<0.05). The circulating Alarin level had a linear regression relationship with BMI, FBG, and HOMA-IR, among which HOMA-IR had the greatest influence on the circulating Alarin level (P<0.05).@*CONCLUSIONS@#There is a significant increase in the circulating Alarin level in obese children, which may be associated with the development of obesity and IR.

High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome.

BACKGROUND/AIMS: Alarin has been reported to be related with increased food intake and body weight. The relationship of circulating Alarin with insulin resistance or metabolic syndrome (MetS), however, is unknown. This study aimed to investigate the physiological role of Alarin and its association with MetS in humans. METHODS: Newly diagnosed MetS patients (n=237) and age-matched healthy subjects (n=192) were recruited for this study. Oral glucose tolerance test, treadmill exercise, lipid infusions and euglycemic-hyperinsulinemic clamp (EHCs) were performed. Circulating Alarin and TNFα levels were measured by ELISA. RESULTS: Circulating Alarin levels were significantly higher in MetS patients compared with healthy subjects (0.46 ± 0.22 vs. 0.41 ± 0.14 µg/L, P < 0.01). In all studied subjects, circulating Alarin levels were positively correlated with WC, blood pressure, FBG, triglyceride, HbA1c, HOMA-IR, AUCglucose, and TNFα (P < 0.05 or P < 0.01). Multivariate logistic regression analyses revealed that circulating Alarin levels were correlated with MetS and insulin resistance. There was no significant change of circulating Alarin levels in the subjects with treadmill exercise for 45 min. In healthy individuals, however, glucose challenge, acute hyperglycemia and lipid infusions resulted in increased circulating Alarin levels, while acute hyperinsulinaemia transiently decreased circulating Alarin levels. CONCLUSION: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.