Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The Effects of Dual GLP-1/GIP Receptor Agonism on Glucagon Secretion - A Review

Research output: Contribution to journalReviewResearchpeer-review

DOI

  1. Gel-Based Proteomics of Clinical Samples Identifies Potential Serological Biomarkers for Early Detection of Colorectal Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Methods and guidelines for measurement of glucagon in plasma

    Research output: Contribution to journalReviewResearchpeer-review

  3. Xeno-Free Propagation of Spermatogonial Stem Cells from Infant Boys

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Glucagon Receptor Signaling and Glucagon Resistance

    Research output: Contribution to journalReviewResearchpeer-review

  1. Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Analgesics use and withdrawal in people with dementia - a register-based Danish study and a systematic review

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The Effect of Different Training Intensities on Oxidatively Generated Modifications of Nucleic Acids: A Randomized, Controlled Trial

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  4. Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

The gut-derived incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion. Furthermore, GLP-1 inhibits glucagon secretion when plasma glucose concentrations are above normal fasting concentrations while GIP acts glucagonotropically at low glucose levels. A dual incretin receptor agonist designed to co-activate GLP-1 and GIP receptors was recently shown to elicit robust improvements of glycemic control (mean haemoglobin A1c reduction of 1.94%) and massive body weight loss (mean weight loss of 11.3 kg) after 26 weeks of treatment with the highest dose (15 mg once weekly) in a clinical trial including overweight/obese patients with type 2 diabetes. Here, we describe the mechanisms by which the two incretins modulate alpha cell secretion of glucagon, review the effects of co-administration of GLP-1 and GIP on glucagon secretion, and discuss the potential role of glucagon in the therapeutic effects observed with novel unimolecular dual GLP-1/GIP receptor agonists. For clinicians and researchers, this manuscript offers an understanding of incretin physiology and pharmacology, and provides mechanistic insight into future antidiabetic and obesity treatments.

Original languageEnglish
Article number4092
JournalInternational Journal of Molecular Sciences
Volume20
Issue number17
ISSN1661-6596
DOIs
Publication statusPublished - 22 Aug 2019

    Research areas

  • Dual-agonism, Gastric inhibitory peptide, Glucagon, Glucagon-like peptide 1, Glucose-dependent insulinotropic polypeptide, Incretins, Obesity, Type 2 diabetes

ID: 57856582