In the liver, PPARγ mRNA expression, as well as Akt protein expression and activity, were increased (P < 0.05), whereas fatty acid synthase and carbohydrate response element binding protein were downregulated (P < 0.05), supporting increased insulin sensitivity and reduced lipogenesis in the liver.
AnxA6-KO mice displayed a trend towards improved insulin sensitivity in oral glucose and insulin tolerance tests (OGTT, ITT), which correlated with increased insulin-inducible phosphorylation of protein kinase B (Akt) and ribosomal protein S6 kinase (S6) in liver extracts.
Moreover, endogenous vaspin positively affected insulin signaling by increasing insulin-stimulated phosphorylation of the key mediator protein kinase B (AKT).
Finally, it was observed that in bone, osteocalcin improves insulin resistance by increasing insulin-induced AKT phosphorylation and reducing the expression of genes involved in bone insulin resistance, resulting in increased secretion of uncarboxylated osteocalcin in circulation.
Adipokine secretion and AKT/mTOR activation play important roles in obesity-accelerated breast cancer aggressiveness in addition to hyperinsulinemia, estrogen signaling, and inflammation.
In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 μM) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPARγ, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation.
The expression of insulin receptors was low, but insulin increased tyrosine phosphorylation of both the insulin receptor and insulin receptor substrate (IRS)-1 and activated protein kinase B (PKB).
Chronic TGZ treatment increased insulin-stimulated phosphatidylinositol (PI) 3-kinase activity and membranous protein kinase B/Akt (PKB/Akt) Ser-473 phosphorylation more than 4-fold.