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Review

Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches

by 1,2 and 1,2,*
1
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
2
NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
*
Author to whom correspondence should be addressed.
Biology 2020, 9(12), 473; https://doi.org/10.3390/biology9120473
Received: 26 November 2020 / Revised: 9 December 2020 / Accepted: 10 December 2020 / Published: 16 December 2020
(This article belongs to the Special Issue Mechanistic Insights into the Pathogenesis of Type 2 Diabetes)
When we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes. View Full-Text
Keywords: GIP; GLP-1; incretins; T2DM GIP; GLP-1; incretins; T2DM
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MDPI and ACS Style

Boer, G.A.; Holst, J.J. Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches. Biology 2020, 9, 473. https://doi.org/10.3390/biology9120473

AMA Style

Boer GA, Holst JJ. Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches. Biology. 2020; 9(12):473. https://doi.org/10.3390/biology9120473

Chicago/Turabian Style

Boer, Geke Aline, and Jens Juul Holst. 2020. "Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches" Biology 9, no. 12: 473. https://doi.org/10.3390/biology9120473

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