Figure 7.

Schematic showing a cycle of "PKC-ι hyperactivation and overexpression in hepatocytes of type 2 diabetic humans. This cycle is driven by insulin and dependent on "PKC-ι itself, as well as IRS-2/PI3K, and is therefore, vicious. This cycle in turn drives lipogenic and inflammatory pathways, thereby leading to insulin resistance, dyslipidaemia and other clinical abnormalities. In contrast to "PKC-ι, IRS-1/PI3K-dependent Akt activation is diminished in diabetic hepatocytes, thereby leading to increases in gluconeogenic factors and hyperglycemia. Opposite to hepatic "PKC-ι, muscle "PKC-ι is underexpressed and underactive, and, along with underactive IRS-1/PI3K and Akt, leads to further decreases in glucose tolerance. Note that the overactive hepatic "PKC-ι cycle in liver exacerbates the underactive "PKC-ι cycle in muscle and vice versa.