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To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a "Goldilocks" amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.
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http://dx.doi.org/10.3803/EnM.2023.103 | DOI Listing |
Rev Med Liege
September 2025
Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Liège, Belgique.
Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, recently commercialized and reimbursed in Belgium for the treatment of type 2 diabetes (T2D). Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg as a once-weekly subcutaneous injection), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. Tirzepatide tolerance is almost similar to that of pure GLP-1 receptor agonists, with digestive adverse events, most often during the first weeks after initiation, which justifies the recommendation of progressive titration every four weeks.
View Article and Find Full Text PDFAnnu Rev Pharmacol Toxicol
September 2025
1Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; email:
In light of the success of blockbuster drugs for type 2 diabetes and obesity based on the GLP-1 hormone, drugmakers have concentrated their efforts on developing new and improved variations that address the route of administration, dosing, pathway selectivity, or polypharmacology. While some of these modifications have demonstrated improved efficacy in clinical studies and offered exciting opportunities for treating other diseases, drug-induced shifts to the conformational landscape of target receptors may have consequences for side effects. Our review summarizes advances in the understanding of the biochemistry, pharmacogenomics, and molecular pharmacology of incretins and their cognate receptors.
View Article and Find Full Text PDFDrug Deliv
December 2025
School of Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Obesity is a global health crisis strongly linked to increased risk of type 2 diabetes, cardiovascular diseases, and other metabolic disorders. Glucagon-like peptide-1 (GLP-1) has emerged as an effective macromolecular therapeutic agent for weight management. This study addressed obesity management from three distinct perspectives: enhancing drug dispersion and bioavailability through a novel drug delivery device, extending drug half-life by developing sustained-release formulations, and sustaining the weight loss through implementation of structured dietary protocols.
View Article and Find Full Text PDFFood Res Int
November 2025
Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan. Electronic address:
Dipeptidyl-peptidase (DPP)-IV inhibition by penultimate N-terminus Pro-containing peptides is a promising strategy for Type 2 diabetes (T2D) management, as it prevents the degradation of incretin hormones (DPP-IV substrates) like glucagon-like peptide-1 (GLP-1), thereby prolonging their half-life. However, the stability and bio-accessibility of these peptides are crucial to their efficacy in orally administered therapeutics. We previously identified LPCL and TPFLPDE peptides from tilapia viscera by-products hydrolysates, which exhibited significant DPP-IV inhibition in vitro and in situ while effectively preserving active GLP-1 levels after 2 h treatment in STC-1 cells under basal glucose conditions.
View Article and Find Full Text PDFExp Clin Endocrinol Diabetes
August 2025
Endocrinology and Metabolism, Gazi University, Ankara, Turkey.
Aberrant expression of glucose-dependent insulinotropic peptide receptors (GIPR) might regulate increased steroidogenesis in patients with ACTH-independent cortisol hypersecretion. This study investigated the presence of aberrant GIPR expression in patients with ACTH-independent cortisol hypersecretion and bilateral adrenal adenomas.Patients with bilateral adrenal adenomas, ACTH-independent CS and aberrant GIPR screened via mixed meal test were included.
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