Dipeptidylpeptidase 4 (DPP4) belongs to the S9b gene family of postproline serine peptidases. It acts mostly as a secreted membrane protein, mediating the degradation and inactivation of glucagon-like peptide (GLP)-1 and gastric inhibitory protein (GIP)[3]. Teneligliptin is a DPP4 inhibitor for the treatment of type 2 diabetes. Teneligliptin inhibits human plasma DPP-4 activity and recombinant human DPP-4 activity in a concentration-dependent manner with IC50 of 1.75 nM and 0.889 nM, respectively[4]. In human umbilical vein endothelial cells exposed to high glucose, teneligliptin (0.1, 1.0 and 3.0 µM) promoted the antioxidant response, reduced ROS levels and induced Nrf2-target genes messenger ribonucleic acid expression. It also improved proliferation rates, regulated the expression of cell-cycle inhibitors markers (P53, P21 and P27), and reduced proapoptotic genes (BAX and CASP3), while promoted BCL2 expression[5]. Teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity in ovariectomized (OVX) mice maintained on a high-fat diet[6].
Teneligliptin HBr/氢溴酸替格列汀 细胞实验
Cell Line
Concentration
Treated Time
Description
References
3T3-L1 adipocytes
1, 5, 10 µM
12 hours
With DPP-4 pretreatment for 12 hours, teneligliptin significantly decreased the expression of Xdh by 19%, 30%, and 26% (at 1, 5, and 10 μM concentrations, respectively).
J Diabetes Res. 2016;2016:3201534
Primary human brain microvascular endothelial cells (HBMVECs)
1, 3 mM
24 and 48 hours
Teneligliptin significantly attenuated OGD/R-induced reduction in cell viability and decreased LDH release, indicating its protective effect against ischemia/reperfusion-induced cell death.
RSC Adv. 2020 Jan 22;10(7):3765-3774
Primary mouse cardiomyocytes
2.5 or 5 µM
24 hours
Teneligliptin significantly inhibited high glucose-induced NLRP3 inflammasome activation and increases in myocardial injury indicators (CK-MB, AST), and increased p-AMPK levels.
World J Diabetes. 2024 Apr 15;15(4):724-734
3T3-L1 adipocytes
1, 5, 10 µM
3 hours
Teneligliptin significantly decreased the expression of Xdh by 45%, 35%, and 34% (at 1, 5, and 10 μM concentrations, respectively).
J Diabetes Res. 2016;2016:3201534
Human umbilical vein endothelial cells (HUVECs)
5 µM
48 hours
TE alone or combined with CA promoted increased E-cadherin expression and suppressed VEGF expression.
Int J Mol Sci. 2020 Mar 21;21(6):2164
Activated hepatic stellate cells (Ac-HSCs)
5 µM
48 hours
TE alone or combined with CA significantly attenuated Ac-HSC proliferation as well as TGF-β1 and α1(I)-procollagen mRNA expression.
Int J Mol Sci. 2020 Mar 21;21(6):2164
Teneligliptin HBr/氢溴酸替格列汀 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Fischer 344 rats
Choline-deficient, L-amino acid-defined diet (CDAA)-induced non-alcoholic steatohepatitis (NASH) model
Oral gavage
0.3 mg/kg/day
Once daily for 16 weeks
TE significantly attenuated CDAA diet-induced hepatic fibrogenesis and carcinogenesis by inhibiting HSC activation, angiogenesis, and oxidative stress.
Int J Mol Sci. 2020 Mar 21;21(6):2164
Wistar rats
Streptozotocin-induced diabetic neuropathic pain model
Intrathecal injection
2 µg/h
Continuous for 7 days at a rate of 1 µL/h
Co-infusion of Teneligliptin with morphine significantly attenuated morphine analgesic tolerance in diabetic neuropathic pain rats by restoring the expression of neuroprotective proteins Nrf2 and HO-1 and suppressing microglial cell activation in the spinal dorsal horn.
Antioxidants (Basel). 2023 Jul 24;12(7):1478
Japanese patients with type 2 diabetes
Human patients
Oral
20 mg
Once daily for 4 days
Add-on treatment with teneligliptin significantly improved 24-h mean glucose levels, the proportion of time in normoglycemia, mean amplitude of glycemic excursions, and total area under the curve within 2 h after each meal. The proportion of time in hypoglycemia and hsCRP levels did not increase significantly compared with before teneligliptin. Values of 1,5-AG and GA were significantly improved by treatment with teneligliptin.
Diabetes Technol Ther. 2014 Dec;16(12):840-5
C57BL/6 male mice
Streptozotocin (STZ)-induced diabetic mouse model
Oral
30 mg/kg
Once daily for 4 weeks
Teneligliptin significantly reversed the deterioration of myocardial hypertrophy, cardiac function indicators (fractional shortening, ejection fraction, heart rate), reduced myocardial injury indicators (CK-MB, AST, LDH) levels, and inhibited NLRP3 inflammasome activation and IL-1β release in diabetic mice.
World J Diabetes. 2024 Apr 15;15(4):724-734
ICR mice
MSG/HFD-induced NAFLD model mice
Oral administration in drinking water
30 mg/kg per day
Daily administration for 10 weeks
Teneligliptin improved the histopathological appearance of the liver and decreased intrahepatic triglyceride levels, associated with downregulation of hepatic lipogenesis-related genes due to AMPK activation.
Int J Mol Sci. 2015 Dec 8;16(12):29207-18
C57/BL6 mice
MCAO mouse model
Intraperitoneal injection
30 mg/kg/day
Once daily for 14 days
Teneligliptin significantly reduced brain infarct volume, ameliorated neurological damage, and improved brain permeability by increasing the expression of the tight junction protein occludin.
RSC Adv. 2020 Jan 22;10(7):3765-3774
Male Wistar rats
High-fat diet (HFD)-induced obesity model
Oral
4.0 mg/kg/day
Once daily for 4 weeks
Under the HFD condition, teneligliptin significantly decreased plasma uric acid levels (by 21%) and significantly reduced Xdh expression in epididymal adipose tissue (by 32%).
J Diabetes Res. 2016;2016:3201534
Wistar rats
Partial sciatic nerve transection (PSNT)-induced neuropathic pain model
Intrathecal injection
5 µg/1 µL/h
Continuous for 7 days
Teneligliptin had mild antinociceptive effects against acute pain but remarkable analgesic effects against neuropathic pain. Additionally, Teneligliptin alleviated pain by suppressing spinal astrocyte activation.
Antioxidants (Basel). 2021 Sep 9;10(9):1438
Human
Patients with type 2 diabetes mellitus
Oral
5 mg, 10 mg, 20 mg, 40 mg
Once daily for 12 to 24 weeks
To evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus. Results showed that compared to placebo, teneligliptin at doses of 5 mg, 10 mg, 20 mg, and 40 mg demonstrated better efficacy in reducing HbA1c and fasting plasma glucose (FPG), with acceptable safety.
Front Endocrinol (Lausanne). 2023 Dec 18;14:1282584
Mice
Db/db diabetic mice
Oral
60 mg/kg/day
Once daily for 10 weeks
Teneligliptin alleviated diabetes-related cognitive impairment by inhibiting the ER stress and NLRP3 inflammasome
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