Table 1.
The in vivo and in vitro studies of Hypoglycemic Drugs
| Study Type |
Hypoglycemic Drugs | Model | Dose | Result | Refs |
|---|---|---|---|---|---|
| In vitro | metformin | HUVECs | Metformin(0.5mM, 24 h) |
p-AMPK↑ OGG1↑ ROS↓ |
[111] |
| metformin | CMECs | Metformin (10µM, 100µM, 1000µM, respectively for 24 h) |
Tom70↑ NO↑ ROS↓ GSH↑ |
[112] | |
| DPP-4 inhibitor | Primary HUVECs |
Saxagliptin (0.5µM, 1µM, respectively for 12 h) ox-LDL(100 µg/ml for 24 h.) |
LOX-1↓ ICAM-1,↓ VCAM-1↓ NOX-4↓ |
[114] | |
| DPP-4 inhibitor | HUVECs |
teneligliptin (0.1µM, 1.0µM, 3µM respectively for 21days) |
NOX-4↓ BAX↓ BCL2↑ ROS↓ |
[116] | |
| DPP-4 inhibitor | HUVECs | Sitagliptin(1µM, 48 h) |
p-AMPK↑ ROS↓ |
[115] | |
| GLP-1 | HUVECs | Exenatide(10 µg/ml, 24 h) |
S1PR2↓ IL-1β↓ TNF-α↓ ROS↓ |
[119] | |
| GLP-1 | IMECs | Liraglutide(3nM,10nM,30nM, 100nM respectively for 24 h) |
PKA↑ eNOS↑ |
[121] | |
| GLP-1 | HRECs | Dulaglutide(25nM, 50nM respectively for 24 h) |
SIRT1↑ eNOS↑ PAI-1↓ |
[122] | |
| GLP-1 | HUVECs | Dulaglutide(50nM, 100nM respectively for 48 h) |
SIRT1↑ NLRP3↓ NOX4↓ |
[123] | |
| GLP-1 | HUVECs | Lixisenatide(10nM, 20nM respectively for 24 h) |
ICAM-1↓ VCAM-1↓ eNOS↑ ROS↓ |
[124] | |
| SGLT2 Inhibitor | HBMECs |
empagliflozin (1 µM, for 48 h) |
mtROS↓ | [129] | |
| Thiazolidinediones | HUVECs | Rosiglitazone(1 to 20 µM respectively for 48 h) |
AMPK↑ NOX↓ ROS↓ |
[134] | |
| In vivo | metformin | STZ-induced male ApoE−/−mice, | Metformin (300 mg/kg/day) by drinking water |
p-AMPK↑ Drp1↓ mitochondrial fission↓ |
[110] |
| SGLT2 Inhibitor | STZ-induced male C57BL/6J mice | Dapagliflozin(10 mg/kg/day) by i.g |
ERK1/2↓ cPLA2↓ ROS↓ |
[125] | |
| SGLT2 Inhibitor | C57BL/6 male mice,db/db mice | Dapagliflozin (1 mg/kg/day) for 8 weeks |
SIRT1↑ eNOS↑ ROS↓ |
[126] | |
| SGLT2 Inhibitor | STZ-induced male ApoE−/−mice | Canagliflozin (30 mg/kg/day) by i.g |
NOX2↓ ICAM-1↓ VCAM-1↓ |
[127] | |
| SGLT2 Inhibitor | STZ-induced male ApoE−/−mice | Empagliflozin (10 mg/kg/day) by i.g |
p-AMPK↑ eNOS↑ mtROS↓ |
[128] | |
| GLP-1 | STZ-induced male SD rats | rhGLP-1 (1.5pmol/kg/min) by osmotic pumps |
PKC-β↓ PKA↑ ROS↓ |
[120] | |
| GLP-1 | STZ-induced male SD rats | exenatide(5 µg/kg, twice a day) by i.h |
NOX4↓ VCAM-1↓ |
[118] | |
| Thiazolidinediones | STZ-induced male SD rats | pioglitazone (10 mg/kg) for 4 weeks |
SOD↑ CAT↑ GSH↑ ROS↓ |
[132] | |
| Thiazolidinediones | STZ-induced male C57BL/6J mice | Rosiglitazone(0.15 g/kg) |
HSP22↑ ICAM-1↓ |
[133] |
Abbreviations used are: ↑,upregulation; ↓, downregulation. AMPK, AMP-activated protein kinase; OGG1, 8-Oxoguanine glycosylase; ROS, reactive oxygen species; mtROS, mitochondrial ROS; Tom, translocase of the outer membrane; NO, nitric oxide; GSH, glutathione. DPP-4, dipeptidyl peptidase‑4; SGLT-2, sodium-glucose cotransporter 2; GLP-1, glucagon-like peptide-1. LOX-1, lectin-like ox-LDL receptor- 1; ICAM-1, intercellular cell adhesion molecule-1; VCAM-1, vascular cell adhesion molecule 1; NOX4, nicotinamide adenine dinucleotide phosphate oxidase 4; STZ, Streptozotocin; Drp1, dynamin-related protein 1; TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; PKA, protein kinase A; eNOS, endothelial nitric oxide synthase; SIRT1, Sirtuin1; PAI-1, plasminogen activator inhibitor-1