This is a video presentation of her 2011 Banting lecture where she explains the mechanism whereby glucose causes insulin to be secreted and discusses specific states that can trigger elements of that mechanism to provoke insulin secretion in the absence of glucose (ie: Fasting Insulin).
She makes an interesting case that Insulin resistance is an adaptive state that is protective of the brains energy source when insulin is high.
However, adipose tissue shouldn’t develop insulin resistance, because its role is exactly the protection of other tissues. In my opinion, adipose IR is simply a type of mechanical failure.
Yeah it does appear to be biomechanical not biochemical. Stuffed fat cells behaving badly because all their machinery is compressed.
This is an excellent study. I need to convince Raphi to talk about it soon.
Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation
Actin-GLUT4 studies support this concept.
Disruption of Cortical Actin in Skeletal Muscle Demonstrates an Essential Role of the Cytoskeleton in Glucose Transporter 4 Translocation in Insulin-sensitive Tissues
http://www.jbc.org/lookup/doi/10.1074/jbc.M402697200
Insulin-stimulated GLUT4 Translocation in Adipocytes Is Dependent upon Cortical Actin Remodeling
GLUT4 translocation to the cell membrane requires some structural changes in actin filaments (part of the cytoskeleton). Imagine a huge, swollen fat cell with a huge lipid droplet that fills out 90+ % of the cell. If it swells up beyond a certain level this actin matrix loses its functionality. GLUT4 transporters will simply be unable to move to the cell membrane after an insulin stimulation.