Glucagons and Glucagon-Like Peptides (GLP-1 / GLP-2)
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Glucagons and Glucagon-Like Peptides (GLP-1 / GLP-2)

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Glucagon-like peptide-1 (GLP-1) is a kind of brain-gut peptide secreted by ileal endocrine cells, which is mainly used as the target of typeⅡdiabetes drugs. Because GLP-1 can inhibit gastric emptying and reduce intestinal peristalsis, it is helpful to control food intake and reduce body weight. In a prospective placebo-controlled, randomized, double-blind, cross-over trial of 19 obese patients, subcutaneous administration of GLP-1 increased postprandial satiety and reduced dietary intake by an average of 15%. However, because GLP-1 is a polypeptide, it is a major drawback that it can’t be given orally.

Mode of Action

It has been confirmed that enteropancreatin promotes islet β cells to secrete insulin in a glucose concentration-dependent manner, and reduces islet α cells to secrete glucagon, thus reducing blood glucose. Normal people in the meal, intestinal trypsin began to secrete, and then promote insulin secretion, in order to reduce the fluctuation of postprandial blood glucose. However, in patients with typeⅡdiabetes mellitus, the “enteropancreatin effect” was damaged, which was mainly manifested as the increase of GLP-1 concentration after meal was lower than that of normal subjects, but its effect of promoting insulin secretion and lowering blood glucose was not significantly damaged. Therefore, GLP-1 and its analogues can be used as an important target for the treatment of typeⅡ diabetes mellitus.

Future

GLP-1 has a variety of functions. However, there are also problems in the application of GLP-1 in clinic, that is, GLP-1 produced by human body is easily degraded by dipeptidyl peptidase IV (DPP- IV) in vivo. Its plasma half-life is less than two minutes, continuous intravenous drip or continuous subcutaneous injection is necessary to produce curative effect, which greatly limits the clinical application of GLP-1. In order to solve this problem, scholars have proposed two schemes, one is to develop GLP-1 analogues to retain the efficacy of GLP-1, but also to resist degradation; the other is to develop DPP- IV inhibitors to prevent the degradation of GLP-1 secreted by the body. At present, some progress has been made in these two aspects. It is believed that with the in-depth study of GLP-1 signaling system, more new targets will be found, so as to develop more new drugs for the treatment of diabetes for the benefit of diabetic patients.

References:
1. Holst, J. J., & Madsbad, S. (2016). Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor. Surgery for Obesity and Related Diseases12(6), 1236-1242.
2. Loidl, G., Neuhaus, B., Schoenleber, R. O., & Stadelmaier, A. (2019). U.S. Patent Application No. 16/086,460.

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