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Cited by 60Diabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review

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Mori, Yusaku, Matsui, Takanori, Hirano, Tsutomu, Yamagishi, Sho-ichi·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21041509PMC PMC7073149
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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans.

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  • In cell cultures, administration of GIP may exert both anti-atherogenic effects and pro-atherogenic effects.

    “In cell cultures, the administration of GIP may exert both anti-atherogenic effects (increased nitric oxide and adiponectin concentration, decreased endothelin-1 levels, reduced oxidative stress, decreased migration and proliferation of fibroblast cells) and pro-atherogenic effects (decreased adiponectin levels, increased endothelin-1 and osteopontin levels) [61].”

    From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [61]

    The Conclusions (section 7) explicitly state that GIP can have both anti- and pro-atherogenic effects in vitro, supporting the central claim. However, the cited sentence’s details go beyond the review: the Cell Culture Studies (sections 2.1–2.3) report increased or unchanged endothelin-1, not decreased endothelin-1, and describe reduced proliferation in vascular smooth muscle cells and reduced migration in monocytes, not both effects in fibroblasts. They report changes in adiponectin gene expression rather than measured adiponectin concentrations. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Mori, Y., Matsui, T., Hirano, T., & Yamagishi, S.-I.
Affiliations
  • SHOWA Medical University (JP)
  • Kurume University (JP)
Corresponding author
Mori, Yusaku
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-02-22
Volume
21
Issue
4
Pages
1509
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21041509
PMC
PMC7073149
OpenAlex
W3008317004
Cited by
60
References
15
Citations by year
2026: 8 · 2025: 13 · 2024: 9 · 2023: 11 · 2022: 8 · 2021: 8 · 2020: 2 · 2018: 1
FWCI
1.11
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • JSPS KAKENHI (16K21370)
  • Taisho Pharmaceutical (No number assigned)
  • Suzuken Memorial Foundation (No number assigned)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
glucose-dependent insulinotropic polypeptide, GIP receptor agonist, atherosclerotic cardiovascular disease, GLP-1 receptor agonists, incretin-based therapy, cardioprotection, type 2 diabetes, anti-obesity, DPP-4 inhibitors, gastrointestinal hormones, insulin secretion
MeSH terms
Insulin Secretion, Animals, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Humans, Enteroendocrine Cells, Atherosclerosis, Dipeptidyl-Peptidase IV Inhibitors

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