グルカゴン様ペプチド-1 glucagon-like peptide 1 glucagon-like peptide-1

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the 7th letter of the Roman alphabet (同)g

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/29 01:42:57」(JST)

Glucagon-like peptide-1 (GLP-1) is an incretin derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. The biologically active forms of GLP-1 are: GLP-1-(7-37) and GLP-1-(7-36)NH2. Those peptides result from selective cleavage of the proglucagon molecule.

GLP-1 secretion by ileal L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogues (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate, protein and lipid. Once in the circulation, GLP-1 has a half-life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4. It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Such glucose-dependent action is particularly attractive because, when the plasma glucose concentration is in the normal fasting range, GLP-1 no longer stimulates insulin to cause hypoglycemia. GLP-1 appears to restore the glucose sensitivity of pancreatic β-cells, with the mechanism possibly involving the increased expression of GLUT2 and glucokinase. GLP-1 is also known to inhibit pancreatic β-cell apoptosis and stimulate the proliferation and differentiation of insulin-secreting β-cells. In addition, GLP-1 inhibits gastric secretion and motility. This delays and protracts carbohydrate absorption and contributes to a satiating effect.

Physiological functions

GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.^[1]^[2]^[3] The known physiological functions of GLP-1 include:

increases insulin secretion from the pancreas in a glucose-dependent manner.
decreases glucagon secretion from the pancreas by engagement of a specific G protein-coupled receptor.
increases insulin-sensitivity in both alpha cells and beta cells
increases beta cells mass and insulin gene expression, post-translational processing and incretion.
inhibits acid secretion and gastric emptying in the stomach.
decreases food intake by increasing satiety in brain.
promotes insulin sensitivity.

As evidence of the physiological role of GLP-1 in post-prandial insulin secretion, it has been shown that an oral dose of glucose triggers a much higher peak in plasma insulin concentration compared to an intravenous dose.

Obese patients undergoing gastric bypass showed marked metabolic adaptations, resulting in frequent diabetes remission 1 year later. When the confounding of calorie restriction is factored out, β-cell function improves rapidly, very possibly under the influence of enhanced GLP-1 responsiveness.^[4]

Outside of its function as an insulin secretagogue, GLP-1 seems also to play a role in bone physiology. Researchers at Universities of Angers and Ulster evidenced a massive reduction in bone strength in GLP-1 receptor knockout mice mainly due to a poor bone quality.^[5]

References

^ "Diabetes and Intestinal Incretin Hormones: A New Therapeutic Paradigm" at medscape.com (slide 36)
^ Toft-Nielsen M, Madsbad S, Holst J (2001). "Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes". J Clin Endocrinol Metab 86 (8): 3853–60. doi:10.1210/jc.86.8.3853. PMID 11502823.
^ Meier J, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck M, Holst J, Schmidt W, Gallwitz B (2004). "Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes". Crit Care Med 32 (3): 848–51. doi:10.1097/01.CCM.0000114811.60629.B5. PMID 15090972.
^ Nannipieri M, Guarino D, Camastra S, Moriconi D, Bellini R, Anselmino M, Ferrannini E (November 2013). "Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: Mechanisms of Diabetes Remission and Role of Gut Hormones". J. Clin. Endocrinol. Metab. 98 (11): 4391–9. doi:10.1210/jc.2013-2538. PMID 24057293
^ Mabilleau G, Mieczkowska A, Irwin N, Flatt PR, Chappard D (2013). "Optimal bone mechanical and material properties require a functional GLP-1 receptor". J Endocrinol 219 (1): 59–68. doi:10.1530/JOE-13-0146. PMID 23911987.

External links

Banting and Best Diabetes Centre at UT glp1
Glucagon-Like Peptide 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

American diabetes association:link-http://diabetes.diabetesjournals.org/content/56/1/8.full

UpToDate Contents

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1. 2型糖尿病治療のためのGlucagon-like peptide-1受容体拮抗剤 glucagon like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus
2. 2型糖尿病の治療のためのジペプチジルペプチダーゼ4（DPP-4）阻害剤 dipeptidyl peptidase 4 dpp 4 inhibitors for the treatment of type 2 diabetes mellitus
3. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus
4. 糖尿病の治療のためのアミリン類似体 amylin analogs for the treatment of diabetes mellitus
5. 肥満の病因 pathogenesis of obesity

English Journal

Effects of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women.

Ueda SY, Miyamoto T, Nakahara H, Shishido T, Usui T, Katsura Y, Yoshikawa T, Fujimoto S.SourceDepartment of Acupuncture, Morinomiya University of Medical Sciences, 1-26-16, Nankokita, Suminoe-ku, Osaka City, Osaka, 559-8611 Japan.
SpringerPlus.Springerplus.2013 Dec;2(1):83. Epub 2013 Mar 5.
The purpose of this study was to investigate the effects of 12 weeks of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women. Twenty healthy middle-aged women were recruited for this study. Several measurements were performed pre and post exercise t
PMID 23504454

Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects.

Murakami M, Une N, Nishizawa M, Suzuki S, Ito H, Horiuchi T.SourceDivision on Endocrinology and Metabolism, Tokyo Metropolitan Health Medical Treatment Corporation Toshima Hospital, Itabashi, Japan.
SpringerPlus.Springerplus.2013 Dec;2(1):20. Epub 2013 Jan 22.
Bile acids play an important role in post-prandial glucose metabolism by stimulating release of glucagon-like peptide-1 (GLP-1) via the G-protein-coupled receptor TGR5, which is expressed in intestinal L cells. Thus, bile acid sequestrants are expected to stimulate secretion of endogenous GLP-1 thro
PMID 23450079

Effects of dietary fatty acid composition from a high fat meal on satiety.

Kozimor A, Chang H, Cooper JA.SourceDepartment of Nutritional Sciences, Texas Tech University, PO Box 41240 Lubbock, TX 79409, USA.
Appetite.Appetite.2013 Oct;69:39-45. doi: 10.1016/j.appet.2013.05.006. Epub 2013 May 18.
The composition of fats within a high-fat (HF) meal may differentially affect hunger and satiety. Purpose: Compare HF meals rich in either monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), or saturated fatty acids (SFAs) on the satiety hormone, peptide YY (PYY), and subjectiv
PMID 23688821

Japanese Journal

膵β細胞におけるGLP-1受容体を介するcAMP制御機構の数理モデル化とシミュレーション研究

竹田有加里,稲垣暢也
内分泌・糖尿病・代謝内科 35(2), 141-148, 2012-08
NAID 40019419110

症例報告インスリン抗体陽性2型糖尿病にGLP-1受容体作動薬が有効で,持続血糖モニターで評価した1例

佐藤愛,大？俊彦,田中聡 [他]
糖尿病 55(6), 398-403, 2012-06
NAID 40019378405

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★リンクテーブル★

国試過去問	「109I025」「110I017」
リンク元	「グルカゴン様ペプチド-1」「glucagon-like peptide 1」「リキシセナチド」「glucagon-like peptide-1」
拡張検索	「GLP-1 analog」
関連記事	「GLP」「G」