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

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  3. Muscle-Saturated Bioactive Lipids Are Increased with Aging and Influenced by High-Intensity Interval Training

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  4. 5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

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  1. Prognostic value of ratio of transmitral early filling velocity to early diastolic strain rate in patients with Type 2 diabetes

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  2. The Liver-α-Cell Axis and Type 2 Diabetes

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  3. Renoprotection with Semaglutide and Liraglutide: Direct or Indirect Effects?

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  4. Endogenous glucose-dependent insulinotropic polypeptide exerts diverging and tissue specific in obese patients with type 2 diabetes

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

ID: 57856582