Table 2.

Metabolic effects of IGF-1

Effect	Mechanism	Experimental model	Reference
IGF-1and lipid metabolism
Stimulation of preadipocyte differentiation	Through IGF-1R receptor activation	In vitro, in vivo: human	[181, 182]
Stimulation of lipogenesis	IGF-1R stimulation, PPAR-γ involved thought	In vitro	[181, 183]
Lipid uptake and oxidation	Promotion of lipid uptake into the muscle and increased lipid oxidation. Not directly demonstrated. Mechanism not yet elucidated	In vivo: mice	[162, 193]
Insulin secretion suppression	IGF-1 seems to inhibit insulin secretion, thus acting on insulin lipogenic effects on fat	In vivo: human	[138, 140, 197, 198]
Reduction of FFA flux in the liver	By suppressing GH secretion (reduce adipose tissue lipolysis) and by augmented lipid utilisation and oxidation		[162, 193, 198]
Reduction in TG and cholesterol levels	In aging animals. Suggesting that IGF-1 could be involved in aging-related MetS	In vivo: aging Wistar rats	[199]
Decreases fat mass in GH deficient patients	Probably secondary to insulin suppression of insulin-induced lipogenesis	In vivo: human	[197]
Normalise lipid transport	Increasing liver expression of genes: pcsk9, lrp; and reducing gene expression of lpl and fabp5	In vivo: Hz (igf+/−) mice with partial IGF-1 deficiency	[164]
Restore lipid metabolism	Increasing liver gene expression of acaa1b, acat1, hmgcst1, hmgrc; reduced in mice with partial IGF-1 deficiency and reverted by replacement therapy	In vivo: Hz (igf+/−) mice with partial IGF-1 deficiency	[164]
IGF-1 and carbohydrate metabolism
Augments energy expenditure	By improving mitochondrial function and protection, thus being able to produce ATP more efficiently with an O/P ratio improved, oxidative damage reduction, protein damage reduction, and calcium handling improvement	In vivo: mice, rats and humans	[105, 106, 108, 200]
Glucose uptake	In muscles through actions on IGF-1R and hybrid receptors	In vitro, in vivo: mice, rat	[133, 161, 162, 171, 172, 201]
	In all peripheral cells through IGF-1R, insulin, and hybrid receptors	In vivo: mice, rat, human	[137, 147, 202– 205]
	Increases placental basal membrane content of GLUT-1	In vitro	[206]
Suppress renal and hepatic gluconeogenesis	High [IGF-1] through its IGF-1 own receptor and hybrid receptors	In vivo: mice, human	[163]
Enhancement of insulin sensitivity and actions	Not only through GH suppression, but IGF-1 directly aiming IR actions through IGF-1R and hybrid receptors	In vitro, in vivo: mice, human	[107, 153, 155, 161, 162, 165– 167, 203, 207– 209, 210, 211]
Increases sugar intestinal transport	Probably by direct effect on enterocyte cytoskeleton, restoring normal position of transporters	In vivo: cirrhotic rats In vitro: in BBV from cirrhotic rats	[110, 194, 195]
Enhances carbohydrate oxidation in patients with GH receptor mutations	Physiologic replacement of IGF-1 improved carbohydrate oxidation	In vivo: humans	[166]
Increases hepatic glucose production in patients with GH receptor mutations	By suppression of insulin, but maintaining overall normoglycaemia	In vivo: humans	[166]
Glucose homeostasis gene modulation	Restores liver gene expression of g6pc, pck1, pdk4, and acly; all them reduced in heterozygous mice with partial IGF-1 deficiency	In vivo: Hz (igf+/−) mice with partial IGF-1 deficiency	[164]

IGF-1 insulin like growth factor 1, PI3K phosphatidylinositol-4,5-bisphosphate 3-kinase, AKT protein kinase B, GLUT1glucose transporter 1, PC pyruvate carboxylase, PEPCK phosphoenolpyruvate carboxykinase, FFA free fatty acids, acaa1b acetyl-CoA acyltransferase 1B, acat 1 acetyl-CoA-sinthetase 1, acly ATP-citrate lyase, fabp1 fatty acid binding protein 1, fabp 5 fatty acid binding protein 5, g6pc glucose-6-phosphatase, pck1 phosphoenolpyruvate-carboxilase, hmgcst 3-hydroxy-3-metilglutarilCoA-sinthetase, hmgrc 3-hydroxy-3-methylglutaryl-CoA reductase, lpl lipoprotein lipase, lrp low density lipoprotein receptor-related protein 1, pcsk9 proproteinconvertase subtilisin/kexin type 9, pdk4 pyruvate deshydrogenase kinase isoenzyme 4