Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

Table 1 Role of AMP-activated protein kinase activation on cell metabolism in different organs

Organ	Effect	Mechanism of action	Ref.
Liver	Inhibition of anabolic pathways	Inhibition of fatty acid synthesis	[27]
		Inhibition of gluconeogenesis
	Stimulation of ATP synthesis	Stimulation of Mitochondrial oxidative phosphorylation	[27]
Skeletal muscle	Regulation of energy expenditure during exercise	Favours the transition from glycolitic to oxidative skeletal muscle fibers	[28]
		Regulation of myocitic uptake and oxidation of fatty acids	[21]
		Enhanced glucose uptake via an increase in GLUT4 expression	[21]
	Increase in skeletal muscle regeneration	Regulation of post-injury inflammatory response	[29]
		Stem cell reprogramming: Induction of proliferation, differentiation and self-renewal	[21]
Bone	Increase in osteoblastogenesis	Increases MSC differentiation towards the osteoblastic lineage favouring Runx2 expression	[30,37]
		Decreases PPARγ expression diminishing MSC differentiation towards the adipocytic phenotype	[36,37]
	Decrease in osteoclastogenesis	Negative regulation of RANKL expression by osteoblasts	[35]

MSC: Mesenchymal stem cells; ATP: Adenosine triphosphate; GLUT4: Glucose transporter type 4; RANKL: Receptor activator for nuclear factor κB ligand.