| 1. |
- Al-Najim, W., et al.
(författare)
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Integrated insights into the role of alpha-melanocyte stimulatory hormone in the control of food intake and glycaemia
- 2018
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 100, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Identifying peptide hormones with multipotent actions on both weight and glycaemia can have a significant impact on therapeutic options in the treatment of obesity and diabetes. This has been exemplified by recent advances involving pharmacological exploitation of glucagon-like peptide 1 biology. Herein, we summarise evidence supporting the potential candidacy in this light of alpha-melanocyte stimulatory hormone, an endogenous peptide hormone and a breakdown product of the neuropeptide pro-opiomelanocortin. We reference its well described central actions in the control of food intake and moreover highlight new data pointing to an important role for this peptide hormone in the periphery, in relation to glycaemic control.
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| 2. |
- Björn, Camilla, et al.
(författare)
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Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r
- 2016
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 81, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing >= 99% of microorganisms in vitro, was in the range of 3-50 mu g/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-alpha) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 mu g/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. (C) 2016 Elsevier Inc. All rights reserved.
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| 3. |
- Gach, Katarzyna, et al.
(författare)
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Synthesis and biological evaluation of novel peripherally active morphiceptin analogs.
- 2010
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Ingår i: Peptides. - Amsterdam : Elsevier BV. - 1873-5169 .- 0196-9781. ; 31:8, s. 1617-1624
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Tidskriftsartikel (refereegranskat)abstract
- Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), a tetrapeptide present in the enzymatic digest of bovine beta-casein, is a selective ligand of the mu-opioid receptor. In the present study, we describe the synthesis of a series of novel morphiceptin analogs modified in positions 1-3. Two of the obtained analogs, [Dmt(1), d-Ala(2), d-1-Nal(3)]morphiceptin and [Dmt(1), d-NMeAla(2), d-1-Nal(3)]morphiceptin (Dmt-2',6'-dimethyltyrosine and d-1-Nal-3-(1-naphthyl)-d-alanine)) displayed very high mu-receptor affinity, resistance to enzymatic degradation, and remarkable supraspinally mediated analgesia, as shown in the hot-plate test after intracerebroventricular but not intravenous administration, which indicated that they could not cross the blood-brain barrier. Therefore, these two analogs were further tested in vitro and in vivo towards their possible peripheral analgesic activity and inhibitory effect on gastrointestinal (GI) motility. We report that both peptides showed strong antinociceptive effect in the writhing test after intraperitoneal administration, inhibited smooth muscle contractility in vitro and GI motility in vivo. Taken together, these findings indicate that the novel morphiceptin analogs which induce peripheral, but not central antinociception, inhibit GI transit, and possess exceptional metabolic stability, may provide an interesting approach to the development of peripherally restricted agents for the treatment of GI motility disorders, such as diarrhea or diarrhea-predominant irritable bowel syndrome.
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| 4. |
- Krieger, Jean-Philippe
(författare)
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Intestinal glucagon-like peptide-1 effects on food intake: Physiological relevance and emerging mechanisms
- 2020
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The gut-brain hormone glucagon-like peptide-1 (GLP-1) has received immense attention over the last couple of decades for its widespread metabolic effects. Notably, intestinal GLP-1 has been recognized as an endogenous satiation signal. Yet, the underlying mechanisms and the pathophysiological relevance of intestinal GLP-1 in obesity remain unclear. This review first recapitulates early findings indicating that intestinal GLP-1 is an endogenous satiation signal, whose eating effects are primarily mediated by vagal afferents. Second, on the basis of recent findings challenging a paracrine action of intestinal GLP-1, a new model for the mediation of GLP-1 effects on eating by two discrete vagal afferent subsets will be proposed. The central mechanisms processing the vagal anorexigenic signals need however to be further delineated. Finally, the idea that intestinal GLP-1 secretion and/or effects on eating are altered in obesity and play a pathophysiological role in the development of obesity will be discussed. In summary, despite the successful therapeutic use of GLP-1 receptor agonists as anti-obesity drugs, the eating effects of intestinal GLP-1 still remain to be elucidated. Specifically, the findings presented here call for a further evaluation of the vago-central neuronal substrates activated by intestinal GLP-1 and for further investigation of its pathophysiological role in obesity.
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| 5. |
- Mantas, Malinauskas, 1985, et al.
(författare)
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Angiotensin IV induced contractions in human jejunal wall musculature in vitro
- 2014
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 59:C, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II (AngII) has been reported to mediate contractile actions in rats and human jejunal wall musculature. However, except for one report showing the Angiotensin IV (AngIV) contractile effects on the internal anal sphincter of rats, no data is available describing the action of AngIV on smooth muscle in human small intestine. The aim of this study was to investigate the expression and localization of the enzymes responsible to AngIV formation, as well as the receptor, and to elucidate the contractile function of AngIV in the muscular layer of human jejunum in vitro. Jejunal smooth muscle was taken from 23 patients undergoing Roux-en-Y gastric bypass surgery and was used to record isometric tension in vitro in response to AngIV alone and in presence of losartan or PD123319. ELISA, western blot and immunohistochemistry were used to investigate the expression and localization of key components for AngIV formation: the enzymes Aminopeptidases-A, B, M, and the AngIV receptor insulin-regulated aminopeptidase (IRAP). AngIV elicited concentration-dependent contraction in both longitudinal and circular smooth-muscle preparation. Presence of losartan abolished AngIV-induced contraction, but not PD123319. The main peptide AngII, as well as the enzymes Aminopeptidase-A, B and M were detected in all muscle samples. Immunohistochemistry localized the enzymes and IRAP in the myenteric plexus between longitudinal and circular muscle layers. The present study indicates that all enzymes necessary for AngIV formation exist in human jejunal smooth muscle and that the contractile action elicited by AngIV is primarily mediated through the AngII type 1 receptor.
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| 6. |
- Miranda, Caroline, et al.
(författare)
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Gap junction coupling and islet delta-cell function in health and disease
- 2022
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 147:January
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Tidskriftsartikel (refereegranskat)abstract
- The pancreatic islets contain beta-cells and alpha-cells, which are responsible for secreting two principal gluco-regulatory hormones; insulin and glucagon, respectively. However, they also contain delta-cells, a relatively sparse cell type that secretes somatostatin (SST). These cells have a complex morphology allowing them to establish an extensive communication network throughout the islet, despite their scarcity. Delta-cells are electrically excitable cells, and SST secretion is released in a glucose- and KATP-dependent manner. SST hyperpolarises the alpha-cell membrane and suppresses exocytosis. In this way, islet SST potently inhibits glucagon release. Recent studies investigating the activity of delta-cells have revealed they are electrically coupled to beta-cells via gap junctions, suggesting the delta-cell is more than just a paracrine inhibitor. In this Review, we summarize delta-cell morphology, function, and the role of SST signalling for regulating islet hormonal output. A distinguishing feature of this Review is that we attempt to use the discovery of this gap junction pathway, together with what is already known about delta-cells, to reframe the role of these cells in both health and disease. In particular, we argue that the discovery of gap junction communication between delta-cells and beta-cells provides new insights into the contribution of delta-cells to the islet hormonal defects observed in both type 1 and type 2 diabetes. This reappraisal of the delta-cell is important as it may offer novel insights into how the physiology of this cell can be utilised to restore islet function in diabetes. © 2021 Elsevier Inc.
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| 7. |
- Nilsson, Ola, 1957, et al.
(författare)
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Human pheochromocytoma cells studied in culture contain large amounts of DSIP-like material.
- 1991
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Ingår i: Peptides. - 0196-9781. ; 12:5, s. 1077-83
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Tidskriftsartikel (refereegranskat)abstract
- Delta sleep-inducing peptide (DSIP)-like immunoreactive (LI) material has been detected in nine different human pheochromocytoma tumors by immunocytochemistry. In primary tumors subjected to indirect immunofluorescence a variable number of tumor cells (25-75%) showed positive cytoplasmic labeling after incubation with DSIP antiserum. Tumor cells grown in culture were strongly labeled by the DSIP antiserum with DSIP-LI concentrated to cell bodies. Electron microscopic immunocytochemistry (immunogold labeling) of pheochromocytoma cells demonstrated DSIP-LI over the dense core of secretory granules. The presence of DSIP-LI in several HPLC fractions from conditioned culture media indicates secretion of DSIP-LI from cultured pheochromocytoma cells. The observations suggest that DSIP-LI is synthesized and stored in secretory granules before release. The different HPLC profiles from each of the tumors may reflect differences in processing or turnover of DSIP-LI in pheochromocytoma cells.
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| 8. |
- Olinski, Robert, et al.
(författare)
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Three insulin-relaxin-like genes in Ciona intestinalis
- 2006
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:11, s. 2535-2546
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Tidskriftsartikel (refereegranskat)abstract
- The Ciona intestinalis genome harbors three insulin-like genes: INS-L1, -L2 and -L3. Conserved synteny between the Ciona-human genomes predicts that Ciona INS-Ls are orthologous to the vertebrate insulin-relaxin family, but this relation cannot be inferred from molecular phylogeny. A conserved protein core with six cysteines; typical arrangement of B-, C- and A-protein domains; pro-protein maturation mode; and putative insulin receptor-binding sites were identified in Ciona INS-L proteins. ESTs used to assemble exonic sequences of INS-Ls combined with qRT-PCR analysis provided evidence that the predicted genes are expressed in the developing and adult Ciona. Our results support that Ciona INS-L1 is orthologous to the vertebrate insulin-like/relaxin genes, INS-L2 to insulin genies and INS-L3 to IGF genes. Our analysis also implies that the insulin-like/relaxin ancestor switched receptor type from tyrosine kinase- to GPCR-type, whereas insulin-IGF subfamily retained the tyrosine kinase-type of receptor. We propose that this receptor-switch occurred after the time when urochordates branched from the common chordate lineage, but before the two genome-duplications at the root of the vertebrates. (c) 2006 Elsevier Inc. All rights reserved.
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| 9. |
- Schéle, Erik, 1980, et al.
(författare)
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Regulation of body fat mass by the gut microbiota: Possible mediation by the brain.
- 2016
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Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 77, s. 54-59
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Forskningsöversikt (refereegranskat)abstract
- New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries in the hypothalamus and brainstem. In this article we will review this study further.
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| 10. |
- Singh, A., et al.
(författare)
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Demystifying functional role of cocaine- and amphetamine-related transcript (CART) peptide in control of energy homeostasis: A twenty-five year expedition
- 2021
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine- and amphetamine-related transcript (CART) is a neuropeptide first discovered in the striatum of the rat brain. Later, the genetic sequence and function of CART peptide (CARTp) was found to be conserved among multiple mammalian species. Over the 25 years, since its discovery, CART mRNA (Cartpt) expression has been reported widely throughout the central and peripheral nervous systems underscoring its role in diverse physiological functions. Here, we review the localization and function of CARTp as it relates to energy homeostasis. We summarize the expression changes of central and peripheral Cartpt in response to metabolic states and make use of available large data sets to gain additional insights into the anatomy of the Cartpt expressing vagal neurons and their expression patterns in the gut. Furthermore, we provide an overview of the role of CARTp as an anorexigenic signal and its effect on energy expenditure and body weight control with insights from both pharmacological and transgenic animal studies. Subsequently, we discuss the role of CARTp in the pathophysiology of obesity and review important new developments towards identifying a candidate receptor for CARTp signalling. Altogether, the field of CARTp research has made rapid and substantial progress recently, and we review the case for considering CARTp as a potential therapeutic target for stemming the obesity epidemic.
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