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胰高血糖素:在 2 型糖尿病中的生理和药理功能及病理生理学意义。

Glucagon: Physiological and Pharmacological Functions and Pathophysiological Significance in Type 2 Diabetes.

机构信息

Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.

出版信息

Endocrinol Metab (Seoul). 2024 Feb;39(1):33-39. doi: 10.3803/EnM.2024.1911. Epub 2024 Feb 22.

DOI:10.3803/EnM.2024.1911
PMID:38417825
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10901671/
Abstract

Glucagon has many functions, including the promotion of hepatic glucose production, fatty acid oxidation, thermogenesis, energy consumption, lipolysis, and myocardial contraction, as well as the suppression of lipogenesis, appetite, and gastrointestinal motility. However, it remains unclear which of these functions are physiological and which are pharmacological. Research on glucagon has lagged behind research on insulin because cross-reactivity with glucagon-related peptides in plasma has hindered the development of an accurate measurement system for glucagon. We recently developed a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) that is more specific and more sensitive to glucagon than the currently used measurement systems. The new sandwich ELISA is expected to contribute to personalized medicine for diabetes through its use in clinical examinations, the diagnosis of the pathophysiological condition of individual diabetes patients, and the choice of a treatment strategy. Efforts are continuing to develop glucagon/glucagon-like peptide-1 receptor dual agonists to improve obesity and fatty liver by enhancing glucagon's appetite-suppressing and lipolysis- and thermogenesis-promoting effects. Thus, glucagon is expected to be applied to new diagnostic and therapeutic strategies based on a more accurate understanding of its functions.

摘要

胰高血糖素具有多种功能,包括促进肝葡萄糖生成、脂肪酸氧化、产热、能量消耗、脂肪分解和心肌收缩,同时抑制脂肪生成、食欲和胃肠蠕动。然而,目前尚不清楚这些功能中哪些是生理性的,哪些是药理学的。由于与血浆中胰高血糖素相关肽的交叉反应,胰高血糖素的研究滞后于胰岛素的研究,这阻碍了对胰高血糖素进行准确测量系统的开发。我们最近开发了一种新的胰高血糖素夹心酶联免疫吸附测定法(ELISA),与目前使用的测量系统相比,该方法对胰高血糖素具有更高的特异性和灵敏度。新的夹心 ELISA 有望通过在临床检查中的应用、个体糖尿病患者病理生理状况的诊断以及治疗策略的选择,为糖尿病的个体化治疗做出贡献。目前正在努力开发胰高血糖素/胰高血糖素样肽-1 受体双重激动剂,通过增强胰高血糖素的抑制食欲、促进脂肪分解和产热作用来改善肥胖和脂肪肝。因此,预计胰高血糖素将基于对其功能的更准确理解,应用于新的诊断和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/2cf1c3cf93fe/enm-2024-1911f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/cc77b22ebd93/enm-2024-1911f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/b0b1f79bce36/enm-2024-1911f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/ba172ae11a59/enm-2024-1911f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/489998e43cc8/enm-2024-1911f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/2cf1c3cf93fe/enm-2024-1911f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/cc77b22ebd93/enm-2024-1911f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/b0b1f79bce36/enm-2024-1911f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/ba172ae11a59/enm-2024-1911f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/489998e43cc8/enm-2024-1911f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e3/10901671/2cf1c3cf93fe/enm-2024-1911f5.jpg

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本文引用的文献

1
A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease.一项评估 efinopegdutide 在非酒精性脂肪性肝病患者中的疗效和安全性的 IIa 期主动对照研究。
J Hepatol. 2023 Oct;79(4):888-897. doi: 10.1016/j.jhep.2023.05.013. Epub 2023 Jun 22.
2
A newly developed glucagon sandwich ELISA is useful for more accurate glucagon evaluation than the currently used sandwich ELISA in subjects with elevated plasma proglucagon-derived peptide levels.一种新开发的胰高血糖素夹心 ELISA 比目前用于检测升高的胰高血糖素原衍生肽水平的夹心 ELISA 更能准确地评估胰高血糖素。
J Diabetes Investig. 2023 May;14(5):648-658. doi: 10.1111/jdi.13986. Epub 2023 Feb 2.
3
Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study.在非 2 型糖尿病肥胖个体中胰高血糖素样肽-1/胰高血糖素受体双重激动剂 JNJ-64565111 的疗效和安全性:一项随机剂量范围研究。
Clin Obes. 2021 Apr;11(2):e12432. doi: 10.1111/cob.12432. Epub 2021 Jan 21.
4
Pseudo-hyperglucagonemia was observed in pancreatectomized patients when measured by glucagon sandwich enzyme-linked immunosorbent assay.假性高胰高血糖素血症在经胰切除术患者中通过胰高血糖素夹心酶联免疫吸附测定法测量时被观察到。
J Diabetes Investig. 2021 Feb;12(2):286-289. doi: 10.1111/jdi.13325. Epub 2020 Jul 17.
5
Plasma glucagon levels measured by sandwich ELISA are correlated with impaired glucose tolerance in type 2 diabetes.夹心 ELISA 法测定的血浆胰高血糖素水平与 2 型糖尿病患者糖耐量受损相关。
Endocr J. 2020 Sep 28;67(9):903-922. doi: 10.1507/endocrj.EJ20-0079. Epub 2020 May 23.
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SGLT1 in pancreatic α cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels.SGLT1 在胰腺 α 细胞中调节小鼠的胰高血糖素分泌,这可能解释了 SGLT2 抑制剂对血浆胰高血糖素水平的不同影响。
Mol Metab. 2019 Jan;19:1-12. doi: 10.1016/j.molmet.2018.10.009. Epub 2018 Oct 27.
7
MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study.在 2 型糖尿病肥胖或超重患者中,GLP-1 和胰高血糖素受体双重激动剂 MEDI0382 的随机、对照、双盲、递增剂量和 2a 期研究。
Lancet. 2018 Jun 30;391(10140):2607-2618. doi: 10.1016/S0140-6736(18)30726-8. Epub 2018 Jun 23.
8
Accurate analytical method for human plasma glucagon levels using liquid chromatography-high resolution mass spectrometry: comparison with commercially available immunoassays.使用液相色谱-高分辨率质谱法测定人血浆胰高血糖素水平的准确分析方法:与市售免疫测定法的比较
Anal Bioanal Chem. 2017 Oct;409(25):5911-5918. doi: 10.1007/s00216-017-0534-0. Epub 2017 Aug 12.
9
Postabsorptive hyperglucagonemia in patients with type 2 diabetes mellitus analyzed with a novel enzyme-linked immunosorbent assay.采用新型酶联免疫吸附试验分析 2 型糖尿病患者的餐后高胰高血糖素血症。
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Diabetologia. 2014 Sep;57(9):1919-26. doi: 10.1007/s00125-014-3283-z. Epub 2014 Jun 3.