Hyperlipidemic Insulin Clamp Dynamics Simulator

Infusion & Clamp Controls

Lipid Emulsion Rate 1.5 mL/min

Target Clamp Glucose 90 mg/dL

Hyperinsulinemic State 100 mU/m²/min

Real-Time Telemetry

Plasma FFA

1.85 mmol/L

Baseline: 0.30

Glucose Infusion (GIR)

3.2 mg/kg/min

Euglycemic Clamp

Disposal (M-Value)

3.2 mg/kg/min

-68.4% Suppression

GLUT4 Translocation

32.1%

PKC-θ Active

Hypothesis Model

Signal Transduction Block: Intracellular fatty acid flux generates Diacylglycerol (DAG), activating PKC-θ. Activated PKC-θ causes Serine-307 phosphorylation of IRS-1, uncoupling insulin receptor signaling and blocking GLUT4 vesicle translocation to the sarcolemma.

Clamp Status & Consequence

Running 6h Lipid Protocol: Plasma FFA reached 1.85 mmol/L, driving 68.4% reduction in glucose disposal rate (M-value: 3.2 mg/kg/min) via GLUT4 blockade.

Fatty Acids (FFA / DAG)

Active PKC-θ / Phospho-IRS1

GLUT4 Translocation Vesicles

Sarcolemma / Glucose Channel

Elapsed Time:

06.0 hrs

Plasma FFA & Intracellular DAG

mM vs Relative Concentration

Glucose Infusion Rate (GIR) & M-Value

mg/kg/min over time

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