Ghrelin (human)
(Synonyms: 来诺瑞林) 目录号 : GC16346
人类胃泌素（Ghrelin）是从人类和大鼠肠道中分离出来的内源性生长激素分泌素受体（GHS-R）的配体，并对弧形神经元活动产生影响，其亲和力比GHSR拮抗剂（D-Lys3）-GHRP-6强得多（IC50为0.3×10-9M，0.9×10-6M）。
Cas No.:258279-04-8
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
Human stromovascular fraction cells (SVFCs) |
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Preparation Method |
Adipocyte differentiation was initiated when cells reached ∼80-90% confluence. Cells were stimulated with differentiation medium I (adipocyte medium supplemented with 10% NCS, 0.5 mmol l-1 3-isobutyl-1-methylxanthine, 0.1 µmol l-1 dexamethasone and 10 µg ml-1 insulin) for 2 days. Furthermore, the cells were then switched to differentiation medium II (adipocyte medium supplemented with 10% NCS and 10 µg ml-1 insulin) for another 6 days and media were changed every 2 days. Adipocytes were 70-75% differentiated (as determined by morphology) in the eighth day of differentiation. They were incubated for 2 h in a serum-free adipocyte medium and, then, stimulated with different concentrations of acylated Ghrelin (human) or with desacyl ghrelin (0.1, 1, 10, 100 and 1000 pmol l-1) for 48 h. One sample per experiment was used for obtaining control responses in the presence of a solvent. |
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Reaction Conditions |
0.1, 1, 10, 100 and 1000 pmol l-1 for 48 hours |
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Applications |
The addition of acylated and desacyl ghrelin during adipocyte differentiation induced a significant increase in PPARG and SREBF1 transcript levels. |
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References: [1]: RodrÍguez A, GÓmez-Ambrosi J, CatalÁn V, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes[J]. International journal of obesity, 2009, 33(5): 541-552. |
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Ghrelin (human) was isolated from the gut of both human and rat as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), and has an effection on the activity of arcute neurones with a much stronger affinity (IC50, 0.3×10-9M) than GHSR antagonist (D-Lys3)-GHRP-6 (IC50, 0.9×10-6M) [1]. The highest levels of ghrelin are secreted from the X/A - like cells of the oxyntic glands located in the gastric fundus, with lower levels widely distributed throughout the body [2]. Ghrelin is secreted direct into the local gastric circulation and transported to the brain directly, requiring it to either cross the blood-brain barrier via a saturated transport system or via the blood stream to enter areas of the brain that are not protected by the blood-brain barrier [3]. Ghrelin modulates the hypothalamic arcuate nucleus, in an indirect manner, via activation of the vagus nerve and brain stem nuclei [4]. Ghrelin has a homeostatic role that encompasses multiple areas of the body, with actions that include downregulation of brown adipose tissue thermogenesis [5-7], modulation of non-hypothalamic brain regions producing an increased taste sensation [7] and stimulation of gastric emptying and motility [8]. The actions of ghrelin may contribute to the development of T2DM and obesity [9].
Differentiating visceral adipocytes were exposed to increasing concentrations of acylated (human) and desacyl ghrelin (0.1-1000 pmol l-1) for 48 h, and induced a significant increase in PPARG and SREBF1 transcript levels, the proportion of cells positive for lipid droplets was markedly increased in the presence of both ghrelin forms, compared with the cells in the differentiation medium without ghrelin [10].
References:
[1]. Traebert M, Riediger T, Whitebread S, et al. Ghrelin acts on leptin‐responsive neurones in the rat arcuate nucleus[J]. Journal of neuroendocrinology, 2002, 14(7): 580-586.
[2]. Dixit V D, Schaffer E M, Pyle R S, et al. Ghrelin inhibits leptin-and activation-induced proinflammatory cytokine expression by human monocytes and T cells[J]. The Journal of clinical investigation, 2004, 114(1): 57-66.
[3]. Angelidis G, Valotassiou V, Georgoulias P. Current and potential roles of ghrelin in clinical practice[J]. Journal of endocrinological investigation, 2010, 33(11): 823-838.
[4]. Date Y, Murakami N, Toshinai K, et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats[J]. Gastroenterology, 2002, 123(4): 1120-1128.
[5]. Tsubone T, Masaki T, Katsuragi I, et al. Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice[J]. Regulatory peptides, 2005, 130(1-2): 97-103.
[6]. Whittle A J, LÓpez M, Vidal-Puig A. Using brown adipose tissue to treat obesity-the central issue[J]. Trends in molecular medicine, 2011, 17(8): 405-411.
[7]. Mano-Otagiri A, Iwasaki-Sekino A, Nemoto T, et al. Genetic suppression of ghrelin receptors activates brown adipocyte function and decreases fat storage in rats[J]. Regulatory peptides, 2010, 160(1-3): 81-90.
[8]. Masuda Y, Tanaka T, Inomata N, et al. Ghrelin stimulates gastric acid secretion and motility in rats[J]. Biochemical and biophysical research communications, 2000, 276(3): 905-908.
[9]. MÜller T D, Nogueiras R, Andermann M L, et al. Ghrelin[J]. Molecular metabolism, 2015, 4(6): 437-460.
[10]. RodrÍguez A, GÓmez-Ambrosi J, CatalÁn V, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes[J]. International journal of obesity, 2009, 33(5): 541-552.
人类胃泌素（Ghrelin）是从人类和大鼠肠道中分离出来的内源性生长激素分泌素受体（GHS-R）的配体,并对弧形神经元活动产生影响,其亲和力比GHSR拮抗剂（D-Lys3）-GHRP-6强得多（IC50为0.3×10-9M,0.9×10-6M）[1]。胃泌素最高水平的分泌源是位于胃底部酸性腺中的X/A-类细胞,较低水平的分布广泛在全身[2]。胃泌素直接分泌到局部胃循环中,并直接输送到大脑,要求它要么通过饱和的转运系统穿越血脑屏障,要么通过血流进入未受血脑屏障保护的脑部区域[3]。胃泌素通过激活迷走神经和脑干核间接地调节下丘脑弧形核[4]。胃泌素具有涵盖身体多个区域的稳态作用,其作用包括下调棕色脂肪组织的热发生[5-7]、调节非下丘脑的脑区产生增加的味觉感觉[7]以及促进胃排空和运动[8]。胃泌素的作用可能有助于2型糖尿病和肥胖的发展[9]。
将分化的内脏脂肪细胞暴露于逐渐增加的酰化（人）和去酰化胃泌素（0.1-1000 pmol / L）浓度中,持续48小时,结果显示与没有酰化胃泌素的分化培养基相比,PPARG和SREBF1转录水平明显增加,呈现出更多的含脂滴细胞比例增加。[10]
| Cas No. | 258279-04-8 | SDF | |
| 别名 | 来诺瑞林 | ||
| 分子式 | C149H249N47O42 | 分子量 | 3370.9 |
| 溶解度 | Soluble in Water | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2967 mL | 1.4833 mL | 2.9666 mL |
| 5 mM | 0.0593 mL | 0.2967 mL | 0.5933 mL |
| 10 mM | 0.0297 mL | 0.1483 mL | 0.2967 mL |
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The Homeostatic Force of Ghrelin
Ghrelin, a gastric-derived acylated peptide, regulates energy homeostasis by transmitting information about peripheral nutritional status to the brain, and is essential for protecting organisms against famine. Ghrelin operates brain circuits to regulate homeostatic and hedonic feeding. Recent research advances have shed new light on ghrelin's multifaceted roles in cellular homeostasis, which could maintain the internal environment and overcome metaflammation in metabolic organs. Here, we highlight our current understanding of the regulatory mechanisms of the ghrelin system in energy metabolism and cellular homeostasis and its clinical trials. Future studies of ghrelin will further elucidate how the stomach regulates systemic homeostasis.
Ghrelin: much more than a hunger hormone
Purpose of review: Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recent literature indicates that the functions of ghrelin go well beyond its role as an orexigenic signal. Here, we have reviewed some of the most recent findings on ghrelin and its signalling in animals and humans.
Recent findings: Ghrelin regulates glucose homeostasis by inhibiting insulin secretion and regulating gluconeogenesis/glycogenolysis. Ghrelin signalling decreases thermogenesis to regulate energy expenditure. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates bone formation and metabolism by modulating proliferation and differentiation of osteoblasts.
Summary: In addition to ghrelin's effects on appetite and adiposity, ghrelin signalling also plays crucial roles in glucose and energy homeostasis, cardioprotection, muscle atrophy and bone metabolism. These multifaceted roles of ghrelin make ghrelin and GHS-R highly attractive targets for drug development. Ghrelin mimetics may be used to treat heart diseases, muscular dystrophy/sarcopenia and osteoporosis; GHS-R antagonists may be used to treat obesity and insulin resistance.
Ghrelin regulation of glucose metabolism
The a 28-amino acid peptide ghrelin was discovered in 1999 as a growth hormone (GH) releasing peptide. Soon after its discovery, ghrelin was found to increase body weight and adiposity by acting on the hypothalamic melanocortinergic system. Subsequently, ghrelin was found to exert a series of metabolic effects, overall testifying ghrelin a pleiotropic nature of broad pharmacological interest. Ghrelin acts through the growth hormone secretagogue-receptor (GHS-R), a seven transmembrane G protein-coupled receptor with high expression in the anterior pituitary, pancreatic islets, thyroid gland, heart and various regions of the brain. Among ghrelins numerous metabolic effects are the most prominent the stimulation of appetite via activation of orexigenic hypothalamic neurocircuits and the food-intake independent stimulation of lipogenesis, which both together lead to an increase in body weight and adiposity. Ghrelin effects beyond the regulation of appetite and GH secretion include the regulation of gut motility, sleep-wake rhythm, taste sensation, reward seeking behaviour, and the regulation of glucose metabolism. The latter received recently increasing recognition because pharmacological inhibition of ghrelin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes. In this review we highlight the multifaceted nature of ghrelin and summarize its glucoregulatory action and discuss the pharmacological value of ghrelin pathway inhibition for the treatment of glucose intolerance and type 2 diabetes.
Hunger, ghrelin and the gut
Hunger is defined as a craving or urgent need for food. Abundant evidence now indicates that homeostatic and cognitive mechanisms promote the sensation of hunger. Communication between the gastrointestinal (GI) tract and the central nervous system (CNS) regulate both homeostatic and cognitive mechanisms to control feeding behavior. In this context the GI derived feeding peptide ghrelin, targets the CNS to promote food anticipation, learning, hedonic feeding and motivation for food. Importantly meal expectation following nutrient deprivation or satiation is associated with elevation of plasma ghrelin, highlighting the propensity of each mechanism to stimulate GI ghrelin secretion. It is well established that multiple physiological processes control ghrelin secretion from the GI tract. For example activation of descending sympathetic and parasympathetic pathways, GI feeding peptides, metabolic factors and endocannabinoid signaling mechanisms all regulate ghrelin secretion. In parallel, activation of the CNS ghrelin receptor (GHSR-1a) controls food anticipation, food-based learning, spatial learning and the rewarding properties of food. Notably GHSR-1a is expressed within a network of CNS regions that regulate diverse aspects of feeding behavior. These examples suggest a redundancy regarding mechanisms that control GI ghrelin secretion and complexity for GHSR-1a-mediated regulation of food intake. Based on this collective data, we suggest that learned information linked to the receipt of food is transmitted from the CNS to the GI tract to stimulate ghrelin release. We further postulate that GI ghrelin release and ghrelin-GHSR-1a interactions adapt over time, metabolic status and environment to direct feeding behavior.
Physiological significance of ghrelin in the cardiovascular system
Ghrelin, a growth hormone-releasing peptide first discovered in rat stomach in 1999, is a ligand for the growth hormone secretagogue receptor. It participates in the regulation of diverse processes, including energy balance and body weight maintenance, and appears to be beneficial for the treatment of cardiovascular diseases. In animal models of chronic heart failure, ghrelin improves cardiac function and remodeling; these findings have been recapitulated in human patients. In other animal models, ghrelin effectively diminishes pulmonary hypertension. Moreover, ghrelin administration early after myocardial infarction decreased the frequency of fatal arrhythmia and improved survival rate. In ghrelin-deficient mice, endogenous ghrelin protects against fatal arrhythmia and promotes remodeling after myocardial infarction. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system have not been fully elucidated, its beneficial effects appear to be mediated through regulation of the autonomic nervous system. Ghrelin is a promising therapeutic agent for cardiac diseases.