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微量胰高血糖素抑制⁺ 活化和Mg²⁺ 依赖性ATP酶活性和Ca²⁺ 以比胰高血糖素高1000倍的效率在肝质膜中转运。它可能是参与抑制肝脏Ca²的活性肽⁺ 抽水机微量胰高血糖素是胰高血糖原的最终加工产物，是胰岛生理的调节因子。

Miniglucagon inhibited both the Ca²⁺ activated and Mg²⁺ dependent ATPase activity and Ca²⁺ transport in liver plasma membranes with an efficiency 1000-fold higher than that of glucagon. It is likely to be the active peptide involved in the inhibition of the liver Ca²⁺ pump. Miniglucagon, the ultimate processing product of proglucagon, is a regulator of the pancreatic islet physiology.

Glucagon是由胰腺分泌的一种肽类激素，氨基酸序列为NH2-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-COOH，可增加体内血糖水平。胰高血糖素的作用与胰岛素相反，胰岛素可以降低血糖含量。促分泌素可诱导胰岛素释放，Miniglucagon（胰高血糖素19-29）通过钙离子途径高效的抑制这个过程。Miniglucagon是胰岛生理学的一种新型的局部调节剂。在2型糖尿病中观察到，这种肽在β细胞中诱导的异常抑制可导致胰岛素分泌受损。Miniglucagon是胰高血糖素正性肌力作用的一种成分。证据表明，胰高血糖素在心脏收缩过程中发挥正性肌力作用，胰高血糖素转变成miniglucagon的过程对于正向肌力作用的产生是必不可少的。

参考文献：

1. Reece J, Campbell N (2002). Biology. San Francisco: Benjamin Cummings. ISBN 0-8053-6624-5.

2. Stéphane Dalle, Ghislaine Fontés, Anne-Dominique Lajoix2, Laurence LeBrigand, René Gross, Gérard Ribes, Michel Dufour, Léo Barry, Dung LeNguyen and Dominique Bataille, Miniglucagon (Glucagon 19-29) A Novel Regulator of the Pancreatic Islet Physiology, doi:10.2337/diabetes.51.2.406Diabetes February 2002 vol. 51 no. 2406-412

3. Pavoine C, Brechler V, Kervan A, Blache Kervan, Le-Nguyen D, Laurent S, Bataille D, Pecker F (1991) Miniglucagon [glucagon-(19-29)] is a component of the positive inotropic effect of glucagon. Am J Physiol 260:C993–C999.

Peptide H-AQDFVQWLMNT-OH is a Research Peptide with significant interest within the field academic and medical research. Recent citations using H-AQDFVQWLMNT-OH include the following: Glucagon-(19-29), a Ca2+ pump inhibitory peptide, is processed from glucagon in the rat liver plasma membrane by a thiol endopeptidase. P Blache , A Kervran, M Dufour, J Martinez - Journal of Biological , 1990 - ASBMBhttps://www.jbc.org/article/S0021-9258(18)45769-9/abstract

胰高血糖素(Glucagon)的定义

胰高血糖素是众所周知的一种胰岛分泌的肽激素，它参与葡萄糖代谢的控制。

Glucagon is best known as a peptide hormone secreted from pancreatic islets that participates in control of glucose metabolism.

胰高血糖素(Glucagon)的相关肽

胰高血糖素被合成为胰高血糖素，并经蛋白水解加工以在胰岛的α细胞内产生胰高血糖素。胰高血糖素原也在肠内表达，在那里它不被加工成胰高血糖素，而是被加工成胰高血糖素样肽家族。在胰腺和肠道中，都会产生三种类型的产品：

Glucagon is synthesized as proglucagon and proteolytically processed to yield glucagons within alpha cells of the pancreatic islets. Proglucagon is also expressed within the intestinal tract, where it is processed not into glucagon, but to a family of glucagon-like peptides. In both pancreas and gut, three types of products are generated:

1、具有已知生物学活性的肽：胰高血糖素和胰高血糖素样肽1（GLP-1）

Peptides with known biological activity: glucagon and glucagon-like peptide-1 (GLP-1)

2、可能具有生物学活性，但表征不佳或仅在非生理浓度下才具有活性的肽：胰高血糖素样肽2（GLP-2）和胃泌酸调节素

Peptides that may have biological activity, but which are poorly characterized or active only at what are considered non-physiologic concentrations: glucagon-like peptide-2 (GLP-2) and oxyntomodulin

3、没有明显生物学活性的肽：glicentin，与glicentin相关的胰肽，主要胰高血糖素原片段【1】。

Peptides without apparent biological activity: glicentin, glicentin-related pancreatic peptide, major proglucagon fragment【1】.

胰高血糖素(Glucagon)的发现

胰高血糖素最初由罗切斯特大学的CP Kimball和John R. Murlin于1923年纯化。胰高血糖素的氨基酸序列在1950年代后期进行了描述【2】。

Glucagon was initially purified by C. P. Kimball and John R. Murlin of the University of Rochester in 1923. The amino acid sequence of glucagon was described in the late-1950s2.

胰高血糖素(Glucagon)的结构特征

胰高血糖素是由29个氨基酸组成的线性肽。它的主要序列在脊椎动物中几乎是完全保守的，并且在结构上与肽激素1的促分泌素家族有关【1】。

Glucagon is a linear peptide of 29 amino acids. Its primary sequence is almost perfectly conserved among vertebrates, and it is structurally related to the secretin family of peptide hormones【1】.

胰高血糖素(Glucagon)的行动方式

胰高血糖素通过其在细胞表面的受体发出信号。胰高血糖素 与胰高血糖素受体的细胞外环的结合导致 后者的构象变化，从而导致随后的偶联的G蛋白的活化。 已知至少两类G蛋白 与胰高血糖素受体的信号转导有关并参与其中， 即G s 和G q。G s 的激活导致 腺苷酸环化酶的激活，细胞内cAMP水平的增加，以及 随后蛋白激酶A（PKA）的激活。激活 的G q导致磷脂酶C，生产的激活 肌醇1,4,5-三磷酸，并随后释放细胞内 钙【3】。

Glucagon signals through its receptor on the cell surface. The binding of glucagon to the extracellular loops of the glucagon receptor results in conformational changes of the latter, leading to subsequent activation of the coupled G proteins. At least two classes of G proteins are known to be associated with and involved in the signal transduction of the glucagon receptor, namely Gs and Gq. The activation of Gs leads to activation of adenylate cyclase, increase in intracellular cAMP levels, and subsequent activation of protein kinase A (PKA). The activation of Gq leads to the activation of phospholipase C, production of inositol 1,4,5-triphosphate, and subsequent release of intracellular calcium【3】.

胰高血糖素(Glucagon)的功能

胰高血糖素在葡萄糖代谢和体内平衡中起关键作用。通过增加糖异生和减少糖酵解来调节血糖。胰岛素的反调节激素可响应胰岛素诱导的低血糖而升高血浆葡萄糖水平。在引发和维持糖尿病的高血糖状况中起重要作用。

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.

GLP-1是葡萄糖依赖性胰岛素释放的有效刺激剂。在胃动力和血浆胰高血糖素水平的抑制中起重要作用。可能与胰岛素的作用无关地抑制饱腹感并刺激周围组织中的葡萄糖释放。对肠上皮具有促进生长的活性。还可能通过对LH，TSH，CRH，催产素和加压素分泌的影响来调节下丘脑垂体轴（HPA）。通过刺激胰岛新生和胰岛β细胞增殖来增加胰岛质量。抑制β细胞凋亡。

GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferaton. Inhibits beta cell apoptosis.

GLP-2刺激小肠的生长并上调小肠的绒毛高度，同时伴有隐窝细胞增殖增加和肠细胞凋亡减少。从胃到结肠的胃肠道是GLP-2作用的主要靶标。在养分稳态，通过增强胃肠功能增强养分吸收以及增加养分处置方面起着关键作用。刺激肠内葡萄糖转运并降低粘膜通透性。

GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.

胃泌酸调节素可显着减少食物摄入。抑制人类的胃排空。抑制胃排空可导致胃扩张增加，这可能通过引起饱胀感而引起饱腹感。

Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.

庆大霉素可以调节胃酸分泌和胃-胃-十二指肠的活性。在生命早期可能对肠道粘膜的生长起重要作用【4】。

Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life【4】.

胰高血糖素(Glucagon)的参考文献：

1. Kieffer TJ and Habener JF (1999).  The Glucagon-Like Peptides. Endocrine Reviews, 20 (6),  876-913

2. Jiang G, Zhang BB (2003). Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab., 284(4), E671-8.

3. Kimball CP, Murlin JR (1923). Aqueous extracts of pancreas. III. Some precipitation reactions of insulin. J. Biol. Chem., 58(1), 337

4. Blache P, Kervran A, Bataille D (1988). Oxyntomodulin and glicentin: brain-gut peptides in the rat. Endocrinology, 123(6), 2782-7.