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Dipeptidyl peptidase-4 inhibition protects the liver of insulin-resistant female rats against triglyceride accumulation by suppressing uric acid.

07:00 EST 14th December 2018 | BioPortfolio

Summary of "Dipeptidyl peptidase-4 inhibition protects the liver of insulin-resistant female rats against triglyceride accumulation by suppressing uric acid."

Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated with impaired glucose and lipid metabolism but the mechanisms are elusive. We therefore, hypothesized that DPP-4 inhibition ameliorates COC-induced glucose dysregulation and hepatic triglyceride (TG) accumulation through adenosine deaminase (ADA) /xanthine oxidase (XO) /uric acid-dependent pathway. Female Wistar rats received (po) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel; po) with or without DPP-4 inhibitor (sitagliptin; 100 mg/kg; po) for 8 weeks (n = 6/group). Glucose dysmetabolism was assessed by elevated fasting blood glucose, impaired oral glucose tolerance test and homeostatic model assessment of IR. Treatment with COC led to increased plasma fasting glucose, triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, IR and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic TG, TG/HDL-cholesterol ratio, malondialdehyde, uric acid (plasma; 25.2 ± 0.6 mg/dl; hepatic 128.9 ± 8.0 mg/100 mg tissue), lactate dehydrogenase, DPP-4, ADA and XO (plasma;10.5 ± 1.1 U/L; hepatic 21.2 ± 1.4 U/g protein) activities. Likewise, COC led to reduction in nitric oxide level. However, DPP-4 inhibition significantly ameliorated these alterations induced by COC treatment through suppression of uric acid (plasma; 15.1 ± 1.0 mg/dl, hepatic; 75.6 ± 5.0 mg/100 mg tissue), XO (plasma; 4.1 ± 0.9 U/L, hepatic; 8.7 ± 0.4 U/g protein), ADA and DPP-4 activities suggesting their involvement in glucose dysregulation and hepatic TG accumulation induced by COC treatment. Therefore, DPP-4 inhibition would impact positively on cardiometabolic disorders, at least in part, through XO, ADA and uric acid suppression.

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This article was published in the following journal.

Name: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Pages: 869-877

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Medical and Biotech [MESH] Definitions

Compounds that supress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.

A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.

A purine and quinazoline derivative that functions as an INCRETIN and DIPEPTIDYL-PEPTIDASE IV INHIBTOR. It is used as a HYPOGLYCEMIC AGENT in the treatment of TYPE II DIABETES MELLITUS.

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Cell-surface glycoproteins and serine protease, also known as dipeptidyl-peptidase IV, that plays a role in T-lymphocyte activation. CD26 binds to ADENOSINE DEAMINASE on the T-cell surface.

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