| First Author | Kopietz F | Year | 2021 |
| Journal | Biochem J | Volume | 478 |
| Issue | 3 | Pages | 633-646 |
| PubMed ID | 33493298 | Mgi Jnum | J:305058 |
| Mgi Id | MGI:6510318 | Doi | 10.1042/BCJ20200659 |
| Citation | Kopietz F, et al. (2021) A-769662 inhibits adipocyte glucose uptake in an AMPK-independent manner. Biochem J 478(3):633-646 |
| abstractText | Activation of AMP-activated protein kinase (AMPK) is considered a valid strategy for the treatment of type 2 diabetes. However, despite the importance of adipose tissue for whole-body energy homeostasis, the effect of AMPK activation in adipocytes has only been studied to a limited extent and mainly with the AMP-mimetic 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), which has limited specificity. The aim of this study was to evaluate the effect of the allosteric AMPK activators A-769662 and 991 on glucose uptake in adipocytes. For this purpose, primary rat or human adipocytes, and cultured 3T3-L1 adipocytes, were treated with either of the allosteric activators, or AICAR, and basal and insulin-stimulated glucose uptake was assessed. Additionally, the effect of AMPK activators on insulin-stimulated phosphorylation of Akt and Akt substrate of 160 kDa was assessed. Furthermore, primary adipocytes from ADaM site binding drug-resistant AMPKbeta1 S108A knock-in mice were employed to investigate the specificity of the drugs for the observed effects. Our results show that insulin-stimulated adipocyte glucose uptake was significantly reduced by A-769662 but not 991, yet neither activator had any clear effects on basal or insulin-stimulated Akt/AS160 signaling. The use of AMPKbeta1 S108A mutant-expressing adipocytes revealed that the observed inhibition of glucose uptake by A-769662 is most likely AMPK-independent, a finding which is supported by the rapid inhibitory effect A-769662 exerts on glucose uptake in 3T3-L1 adipocytes. These data suggest that AMPK activation per se does not inhibit glucose uptake in adipocytes and that the effects of AICAR and A-769662 are AMPK-independent. |
