Table 2.
The roles of GLP-1 RAs in aging-related diseases in cultured cells.
| Agents | Diseases | Cell types | Dosing | Duration | Effects | Ref. |
|---|---|---|---|---|---|---|
| GLP-1 | Osteoporosis | Saos-2, TE-85, MG-63 cell lines | / | / | GLP-1 increases the viability levels of MG-63 and TE-85 osteoblastic cell lines. | [72] |
| GLP-1 | Osteoporosis | Saos-2, TE-85 cell lines | / | / | GLP-1 affects bone metabolism possibly through the ATP-induced c-Fos activation. | [73] |
| GLP-1 | Osteoporosis | ADSCs | 10, 100 nM | / | GLP-1 stimulates osteoblast differentiation in ADSCs via ERK signaling pathway, whereas it inhibits adipocyte differentiation. | [75] |
| exendin-4 | Alzheimer’s disease | SH-SY5Y cells, Primary neurons |
0, 50, 100, 200, 500 nM | 2h | Exendin-4 ameliorates the toxicity of Aβ and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. | [89] |
| exenatide | Alzheimer’s disease | Brain ECs | 5nmol/kg/day | 4-5w | Exenatide strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage. | [90] |
| GLP-1 exendin-4 |
Parkinson’s disease | SH-SY5Y cells | / | / | GLP-1 and exendin-4 stimulates cell proliferation and increased cell viability mainly via the PKA and PI3K signaling pathways. | [99] |
| GLP-1 exendin-4 |
Vascular aging | Human umbilical vein ECs | 10 nmol/L | 30min | GLP-1 prevents ROS-induced human umbilical vein endothelial cell senescence through the activation of PKA. | [11] |
| exendin-4 | Vascular aging | VSMCs | / | / | Inhibiting Rac1 activation via a cAMP/PKA-dependent pathway and activating Nrf2 contribute to the protective effects of exendin-4 against ANG II-induced senescence in VSMCs. | [104, 105] |
| liraglutide | Atherosclerosis | Human THP-1 macrophages, bone marrow-derived macrophages |
250 nmol/l | 6h | Liraglutide decreases inflammatory response in MΦ0 THP-1 macrophages and bone marrow-derived macrophages | [117] |
| liraglutide | Atherosclerosis | VMSCs | 100 nM / 1 μM | 120h | Liraglutide may inhibit Ang II-induced VSMC proliferation by activating AMPK signaling and inducing cell cycle arrest, thus delaying the progression of atherosclerosis | [120] |
| exendin-4 | Hypertension | LLC-PK1 cell line | 1nM | 30min | Exendin-4 regulates Na+/H+ exchanger NHE3 in renal proximal tubule cells. | [134] |
| exendin-4 | Kidney diseases | HK-2 cells | 0, 0.1, 1, 10, 100?nM | 48h | Exendin-4 ameliorates high glucose-induced fibrosis by inhibiting the secretion of miR-192 from injured renal tubular epithelial cells. | [13] |
| exendin-4 | Kidney diseases | MCs | 0.1, 1, 10, 100nM | 12,24,48 h | Exendin-4 alleviates high glucose-induced rat MC dysfunction through the AMPK pathway. | [147] |
| liraglutide | Osteoarthritis | Chondrocytes | 100/500nM | 24h | Liraglutide protects chondrocytes against endoplasmic reticulum stress and apoptosis induced by IL-1β or TGs. | [166] |
| liraglutide | Osteoarthritis | Human primary chondrocytes | 50/100 nM | 24h | Liraglutide suppresses TNF-α-induced degradation of extracellular matrix in human chondrocytes. | [167] |
| liraglutide | Sarcopenia | C2C12 cells | 1μM | / | Liraglutide induces myogenesis in C2C12 myoblasts via a cAMP-dependent complex network of signaling events. | [168] |
| exendin-4 | Sarcopenia | C2C12 cells | 20 nM | 60min/6h | Exendin-4 suppresses the expression of MSTN and muscle atrophic factors such as atrogin-1 and MuRF-1 in Dex-treated C2C12 myotubes. | [169] |
ADSCs: adipose-derived stem cells; ANG: angiotensin; atrogin-1: F-box only protein 32; BBB: blood brain barrier; Dex: dexamethasone; ECs: endothelial cells; MCs: mesangial cells; MSTN: myostatin; MuRF-1: muscle RING-finger protein-1; TGs: triglycerides.