Table 2 Metabolic effects of IGF-1

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]