Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes

Rufinatscha, Kerstin; Radlinger, Bernhard; Dobner, Jochen; Folie, Sabrina; Bon, Claudia; Profanter, Elisabeth; Ress, Claudia; Salzmann, Karin; Staudacher, G; Tilg, Herbert; Kaser, Susanne

doi:10.1016/j.bbrc.2017.02.071

Cited by 23 publications

(21 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Next to the key role of ADA in T-cell activity and insulin resistance, it is bound on the cell surface by CD26 protein (DPP-4) that is an important modulator of insulin secretion. [ 165 ] DPP-4 (dipeptidyl peptidase-4) poses an enzymatic activity of ectopeptidase and rapidly degrades various peptides, including glucagon-like peptide-1, an incretin that promotes insulin secretion by pancreatic beta cells, inhibits glucagon secretion in alpha cells, decreases the gastric discharge rate, and mediates appetite suppression [ 166 ]. CD26 is abundantly expressed on mammalian endothelial, epithelial and immune cells and represents increased levels in T2DM alongside with ADA.…”

Section: Cardiovascular Pathologies Associated With Increased Ada mentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

View full text Add to dashboard Cite

Adenosine deaminase (ADA) is an enzyme of purine metabolism that irreversibly converts adenosine to inosine or 2′deoxyadenosine to 2′deoxyinosine. ADA is active both inside the cell and on the cell surface where it was found to interact with membrane proteins, such as CD26 and adenosine receptors, forming ecto-ADA (eADA). In addition to adenosine uptake, the activity of eADA is an essential mechanism that terminates adenosine signaling. This is particularly important in cardiovascular system, where adenosine protects against endothelial dysfunction, vascular inflammation, or thrombosis. Besides enzymatic function, ADA protein mediates cell-to-cell interactions involved in lymphocyte co-stimulation or endothelial activation. Furthermore, alteration in ADA activity was demonstrated in many cardiovascular pathologies such as atherosclerosis, myocardial ischemia-reperfusion injury, hypertension, thrombosis, or diabetes. Modulation of ADA activity could be an important therapeutic target. This work provides a systematic review of ADA activity and anchoring inhibitors as well as summarizes the perspectives of their therapeutic use in cardiovascular pathologies associated with increased activity of ADA.

show abstract

Section: Cardiovascular Pathologies Associated With Increased Ada mentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, we did not observe a significant downregulation of SREBP1c and a significant upregulation of PPAR-. Rufinatscha et al (2017) reported that DPP-4 knockdown of HepG2 cells reduced liver TG content by significantly reducing the SREBP1c expression level and significantly increasing the PPAR-expression level. The DPP-4 expression level in the liver was not significantly changed in the present study (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Combined treatment of dipeptidyl peptidase‐4 inhibitor and exercise training improves lipid profile in KK/Ta mice

Tanimura

Aoi

Mizushima

et al. 2019

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the central question of this study?Exercise for type 2 diabetes patients treated with insulin therapy involves the risk of hypoglycaemia. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors can be effective in combination with exercise because they reduce the incidence of hypoglycaemia. We evaluated the effect of this combination of treatments on hepatic lipid metabolism in diabetic KK/Ta mice. What is the main finding and its importance?The combination of a DPP‐4 inhibitor and exercise, which lowers the risk of hypoglycaemia, is useful for improving insulin resistance by inhibiting excess insulin secretion and decreasing hepatic lipid accumulation, validated by downregulated CD36. Abstract The role of exercise training in prevention of diabetes and/or dyslipidaemia has been firmly established. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors improve insulin sensitivity and have attracted attention as therapeutics for hepatic lipid accumulation. The effect of a combination of DPP‐4 inhibitor and exercise training on the prevention and treatment of hepatic lipid accumulation is unclear. Here, we investigated whether alogliptin, a DPP‐4 inhibitor, enhances the preventive effect of exercise‐induced hepatic lipid accumulation in diabetic mice. Balb/c and KK/Ta mice were fed a high‐fat diet. Mice were divided into the following five groups: B, Balb/c mice; K, KK/Ta mice; K‐A, KK/Ta mice with alogliptin (0.01%); K‐Ex, KK/Ta mice with exercise training (3 days week−1, 15–20 m min−1 for 30 min); and K‐Ex+A, KK/Ta mice with alogliptin and exercise training (n = 8 or 9 mice per group). After 8 weeks, glucose, insulin and triglyceride concentrations in the blood and triglyceride levels in the liver were significantly lower in the K‐Ex+A group than in the K group. The liver expression level of PPAR‐γ in the K group was significantly higher than that in the other groups. Additionally, the liver CD36 expression level was significantly lower in the K‐Ex+A and B groups than in the K group. Thus, combined therapy of a DPP‐4 inhibitor with exercise training was effective against high‐fat diet‐induced hepatic lipid accumulation in KK/Ta mice. The results of this study provide useful support for the practice of safe exercise therapy even in diabetic patients who require treatment with a DPP‐4 inhibitor.

show abstract

“…Potential side‐effects associated with DPP‐IV inhibitors may result from the inadvertent inhibition of related enzymes, such as DPP‐VIII and DPP‐IX. Therefore, there is an increased focus on identifying natural DPP‐IV inhibitors for the prevention and control of T2D …”

Section: Introductionmentioning

confidence: 99%

Natural Breviscapin, Mangiferin, and a Modified Mangostin Present Inhibitory Effect on Dipeptidyl Peptidase‐IV

et al. 2018

View full text Add to dashboard Cite

Type 2 diabetes was usually caused by inadequate secretion of insulin or insulin resistance in tissues and organs. About 90% diabetes belongs to type 2 diabetes, which is seriously harmful to human health. Dipeptidyl Peptidase‐IV (DPP‐IV) target have attracted much attention because of its ability to prevent type 2 diabetes (T2D). Clinical application of chemical synthetic medicines has different degrees of side effects. Therefore, the present evaluation aims to seek DPP‐IV inhibitors as the source of natural products. DPP‐IV inhibitory activities of eight natural products and a structural modification of mangostin (eight chromone of 1–8 and iridoid glycoside for 9) were evaluated by this manuscript at the enzyme level. As a result, three chromones of 2 (a modified mangostin), 3 (mangiferin) and 5 (breviscapin) showed moderate DPP‐IV inhibitory activities with IC50 values of 69.27 μM, 44.19 μM, and 49.53 μM via the use of the fluorescence‐based method (0.25 mM, 0.34 mM and 0.85 mM for the chromogenic substrate method). This study suggests that natural products, which mainly consist by chromone that generated from Mango and Scutellaria baicalensis may have beneficial effects on treating T2D.

show abstract

Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes

Cited by 23 publications

References 22 publications

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Combined treatment of dipeptidyl peptidase‐4 inhibitor and exercise training improves lipid profile in KK/Ta mice

Natural Breviscapin, Mangiferin, and a Modified Mangostin Present Inhibitory Effect on Dipeptidyl Peptidase‐IV

Contact Info

Product

Resources

About