β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology..., 2019, Crocker et al

Andy · Dec 15, 2019

Full title: β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology in developing C2C12 muscle cells

The serine/threonine kinase AMP-activated protein kinase (AMPK) is a drug target for the treatment of obesity and type 2 diabetes (T2D). Metformin, a widely prescribed anti-hyperglycemic agent, and β-guanidinopropionic acid (β-GPA), a dietary supplement and creatine analog, have been shown to increase activity of AMPK. Macroautophagy is an intracellular degradation pathway for aggregated proteins and dysfunctional organelles, which can be mediated by AMPK.

The present study sought to elucidate how metformin and β-GPA affect cell morphology, AMPK activity, autophagy and mitochondrial morphology and function in developing C2C12 myotubes. β-GPA reduced myotube diameter and increased length throughout differentiation, while metformin increased myotube diameter only at the 48 h time point. β-GPA treatment enhanced AMPK signaling and expression of autophagy-related proteins. β-GPA treatment also increased the density of autophagosomes, autolysosomes, and lysosomes. Metformin also increased activation of AMPK after 48 h, but in contrast to β-GPA, led to a dramatic reduction in the density of autophagosomes and lysosomes. Both metformin and β-GPA reduced the mitochondrial oxygen consumption rate, and differentially altered mitochondrial morphology. Obesity and T2D have been shown to increase mitochondrial dysfunction and reduce autophagic flux in skeletal muscle cells.

Therefore, β-GPA may help to alleviate the effects of metabolic disease by increasing autophagic flux in skeletal muscle cells. In contrast, the reduction of autophagy by metformin may lead to dysregulation of mitochondrial maintenance, as well as muscle development.
Click to expand...

Paywall, https://link.springer.com/article/10.1007/s10974-019-09568-0
Scihub, https://sci-hub.se/10.1007/s10974-019-09568-0

Log in or Sign up

β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology..., 2019, Crocker et al

Andy Committee Member

Share This Page

Log in or Sign up

β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology..., 2019, Crocker et al

Andy Committee Member

Share This Page

Useful Searches