ArticleDiabetologia2014
Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 82 citations in OpenAlex.
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- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- Profiling of proteases involved in SARS-CoV-2 pathogenesis in human saliva: Influence of age and gender.Journal, genetic engineering & biotechnology · 2025Article
- Pharmacokinetic/Pharmacodynamic modelling of Saxagliptin and its active metabolite, 5-hydroxy Saxagliptin in rats with Type 2 Diabetes Mellitus.BMC pharmacology & toxicology · 2024Article
- Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes.Frontiers in endocrinology · 2024Article
- Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins.Obesity (Silver Spring, Md.) · 2023Article
- The human α cell in health and disease.The Journal of endocrinology · 2023Review
- Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress.iScience · 2023Article
- Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.Frontiers in endocrinology · 2023Article
- GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1.The Journal of clinical endocrinology and metabolism · 2022Article
- Roles of glucose-dependent insulinotropic polypeptide in diet-induced obesity.Journal of diabetes investigation · 2022Review
- Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2.Journal of molecular endocrinology · 2022Review
- Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion.Frontiers in endocrinology · 2022Review
- Diabetes and SARS-CoV-2-Is There a Mutual Connection?Frontiers in cell and developmental biology · 2022Review
- Macroalgal protein hydrolysates from Palmaria palmata influence the 'incretin effect' in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion.European journal of nutrition · 2021Article
- Effect ofJournal of diabetes and metabolic disorders · 2021Article
- ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes.Acta physiologica (Oxford, England) · 2021Review
- Association between cardiometabolic risk factors and COVID-19 susceptibility, severity and mortality: a review.Journal of diabetes and metabolic disorders · 2021Review
- A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInhibition of the enzyme dipeptidyl peptidase 4 (DPP-4), which cleaves and inactivates glucagon-like peptide 1 (GLP-1), is a glucose-lowering strategy in type 2 diabetes. Since DPP-4 is a ubiquitously distributed enzyme, we examined whether it is expressed in islets and whether an islet effect to inhibit DPP-4 may result in stimulated insulin secretion.
methodsWe investigated DPP-4 expression and activity in the islets of mouse models of obesity as well as human islets from non-diabetic and type 2 diabetic donors. We further investigated whether inhibition with DPP-4 inhibitors could promote insulin secretion via islet GLP-1 in isolated islets.
resultsDPP-4 was readily detected in mouse and human islets with species-specific cellular localisation. In mice, DPP-4 was expressed predominantly in beta cells, whereas in humans it was expressed nearly exclusively in alpha cells. DPP-4 activity was significantly increased in islets from diet-induced obese mice compared with mice fed a control diet. In humans, DPP-4 activity was significantly lower in islets from type 2 diabetic donors than in non-diabetic donors. In human islets, there was a significant positive correlation between DPP-4 activity and insulin secretory response to 16.7 mmol/l glucose. Treatment of mouse islets with the DPP-4 inhibitors, NVPDPP728 and vildagliptin, resulted in a significant potentiation of insulin secretion in a GLP-1-dependent manner, as this was inhibited by the GLP-1 receptor antagonist, Exendin (9-39), and was retained in glucose-dependent insulinotropic polypeptide (GIP) receptor-deficient mice but lost in mice lacking GLP-1 receptors or both incretin receptors. Human islets treated with the DPP-4 inhibitor, vildagliptin, showed increased secretion of insulin and intact GLP-1. CONCLUSIONS/
interpretationWe conclude that DPP-4 is present and active in mouse and human islets, is regulated by the disease state, and that inhibition of islet DPP-4 activity can have direct effects on islet function. Inhibiting islet DPP-4 activity may therefore contribute to the insulin-secretory and glucose-lowering action of DPP-4 inhibition.
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