Beskrivning
BackgroundAMPK activation is considered a useful strategy for the treatment of type 2 diabetes due to its beneficial effects on lipid and glucose metabolism in muscle and liver cells. For example, it is known that AMPK activation promotes glucose uptake into skeletal muscle, thus clearing high blood glucose levels. Although muscle is the main site for insulin-stimulated glucose uptake, the uptake of glucose into adipocytes appears to be important for whole-body glucose homeostasis. Contrary to the finding in muscle, there is evidence that AICAR-induced AMPK activation in adipocytes causes a reduction in glucose uptake, indicating a distinct regulation of this process in muscle and adipose tissue. However, the exact mechanism underlying this effect of AICAR in adipocytes is still unknown and it has been suggested that the effects on glucose uptake observed with AICAR are at least to some extent AMPK-independent.
Aim
Conclusions about the role of AMPK in adipocyte glucose uptake are primarily based on the usage of AICAR in 3T3L1 or rat adipocytes. Thus, our aim was to employ the more specific, small molecule AMPK activators A-769662 and 991, to first of all re-evaluate the effect of AMPK activation on glucose uptake in primary rat adipocytes. In addition to this frequently used model we also investigated the effect of the three different activators on glucose uptake in primary human adipocytes isolated from subcutaneous tissue.
Results
In agreement with previous findings, pre-treatment with AICAR was shown to reduce basal and insulin-induced glucose uptake in primary rat adipocytes. Furthermore, a similar inhibitory action of AICAR was also observed in primary human adipocytes. In contrast, when treating rat adipocytes with A-769662, instead no changes in glucose uptake were observed. Similarly, preliminary results indicate that 991 induces no changes in glucose uptake in human adipocytes, at least in the basal state. Effects of 991 treatment in rat adipocytes and on insulin-stimulated glucose uptake in human adipocytes are currently under investigation.
Conclusion
In conclusion, the data we generated so far suggests that glucose uptake in adipocytes is not affected by AMPK activation and that AICAR-induced effects on glucose uptake in rat and human cells might be AMPK-independent.
| Period | 2018 okt. 1 |
|---|---|
| Evenemangstitel | AMPK from Mechanisms to New Therapies |
| Typ av evenemang | Konferens |
| Plats | KanadaVisa på karta |
| Omfattning | Internationell |