| Naslov: | Diverse inhibitors of de novo purine synthesis promote AICAR-induced AMPK activation and glucose uptake in L6 myotubes |
|---|
| Avtorji: | ID Dolinar, Klemen (Avtor)
ID Miš, Katarina (Avtor)
ID Šopar, Katja (Avtor)
ID Šutar, Mateja (Avtor)
ID Božič, Meta (Avtor)
ID Kolar, Matic (Avtor)
ID Hropot, Tim (Avtor)
ID Garcia-Roves, Pablo Miguel (Avtor)
ID Chibalin, Alexander V. (Avtor)
ID Pirkmajer, Sergej (Avtor) |
|---|
| Datoteke: |  PDF - Predstavitvena datoteka, prenos (5,17 MB)
MD5: 24ACB96C274A904D8A5CFBF380F72104
 URL - Izvorni URL, za dostop obiščite https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.70037
|
|---|
| Jezik: | Angleški jezik |
|---|
| Tipologija: | 1.01 - Izvirni znanstveni članek |
|---|
| Organizacija: |  UKC LJ - Univerzitetni klinični center Ljubljana
|
|---|
| Povzetek: | Methotrexate, an immunosuppressant and anticancer drug, promotes glucose uptake and lipid oxidation in skeletal muscle via activation of AMP-activated protein kinase (AMPK). Methotrexate promotes AMPK activation by inhibiting 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP) formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), which converts ZMP, an endogenous purine precursor and an active form of the pharmacological AMPK activator AICAR, to IMP during de novo purine synthesis. In addition to methotrexate, inhibition of purine synthesis underpins the therapeutic effects of a number of commonly used immunosuppressive, anticancer, and antimicrobial drugs, raising the question of whether activation of AMPK in skeletal muscle could be a recurrent feature of these drugs. Using L6 myotubes, we found that AICAR-induced AMPK activation and glucose uptake were enhanced by inhibitors of the conversion of IMP to GMP (mycophenolate mofetil) or of IMP to AMP (alanosine) as well as by indirect inhibitors of human (trimetrexate) and bacterial ATIC (sulfamethoxazole). 6-Mercaptopurine, which inhibits the conversion of IMP to GMP and AMP, activated AMPK, increased glucose uptake, and suppressed insulin signaling, but did not enhance the effect of AICAR. As determined by measuring oxygen consumption rate, none of these agents suppressed mitochondrial function. Overall, our results indicate that IMP metabolism is a gateway for the modulation of AMPK and its metabolic effects in skeletal muscle cells. |
|---|
| Ključne besede: | AMP‐activated protein kinase (AMPK), folate metabolism, glucose uptake, insulin signaling, purine metabolism, skeletal muscle cells |
|---|
| Status publikacije: | Objavljeno |
|---|
| Verzija publikacije: | Objavljena publikacija |
|---|
| Leto izida: | 2025 |
|---|
| Št. strani: | str. 1-15 |
|---|
| Številčenje: | Vol. 51, iss. 4, [Article no.] e70037 |
|---|
| PID: | 20.500.12556/DiRROS-28856  |
|---|
| UDK: | 616-092 |
|---|
| ISSN pri članku: | 0951-6433 |
|---|
| DOI: | 10.1002/biof.70037 |
|---|
| COBISS.SI-ID: | 248413955 |
|---|
| Datum objave v DiRROS: | 09.04.2026 |
|---|
| Število ogledov: | 22 |
|---|
| Število prenosov: | 15 |
|---|
| Metapodatki: |    |
|---|
|
:
|
Kopiraj citat |
|---|
| | | | Objavi na: |  |
|---|
Postavite miškin kazalec na naslov za izpis povzetka. Klik na naslov izpiše
podrobnosti ali sproži prenos. |
