Figure 2. Insulin-AKT Signaling Pathway. Insulin will bind to an insulin receptor on a given cell. The receptor will phosphorylate and activate IRS 1/2; which causes the recruitment of PI3K. A now active PI3K will phosphorylate and activate PIP2; causing it to become PIP3 (there is an enzyme not shown here, PTEN, that has the ability to inhibit both IRS 1/2 and PIP3). As PIP3 increases in concentration, it recruits PDK1 and AKT2 towards the cell membrane. PDK1 activates AKT2; which in turn will phosphorylate and inhibit AS160. This inhibition facilitates the translocation of a glucose transporter towards the cell membrane; that of which allows the movement of glucose into cells and increased glycolysis (GLUT-4 is primarily found on adipose tissue and striated muscle cells). Olanzapine may block the phosphorylation of IRS-1, as well as possibly inhibit the functioning of AKT2 activity; preventing glucose transport protein translocation to the cell membrane [5]. AKT2: Protein Kinase 2; AS160: AKT substrate 160; GLUT-4: glucose transporter type 4; IRS: insulin-receptor substrate; PDK1: Phosphoinositide-dependent kinase-1; PI3K:phosphoinositide 3-kinase; PIP2: Phosphatidylinositol 4,5-bisphosphate; PIP3: Phosphatidylinositol 3,4,5-trisphosphate

From

Insulin Resistance One Mechanism Two Presentations: Olanzapine Induced DKA and Hypertriglyceridemia

Louis Costanzo, Chetana Pendkar, Amara Shafi, Joseph Gorga

American Journal of Medical Case Reports. 2021, 9(2), 131-133 doi:10.12691/ajmcr-9-2-8