Insulin's direct action on liver cells is needed to make fat but not to reduce glucose production

Insulin-resistant states such as type II diabetes mellitus (T2DM) show that insulin promotes lipid synthesis while failing to suppress hepatic glucose production.

• Akt-dependent activation of mTORC1 and inhibition of Foxo1 are needed for the production of new fatty acids in the liver.
• Hepatic insulin signaling may remain functional during insulin resistance, contrary to expectations.
• Insulin's ability to lower glucose production in the liver is influenced by a decrease in fat breakdown in fat cells and levels of free fatty acids in the blood.
• This suppression of glucose production does not rely on signals from the vagus nerve or glucagon.
• Excess free fatty acids in circulation may contribute to the inability to suppress glucose production in T2DM.

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