Chain splitting of insulin: an underlying mechanism of insulin resistance?

Despite decades of intense research, the mechanisms underlying insulin resistance are still poorly understood. What if one of the major causes of insulin resistance is not related to defects in the target tissues and/or insulin receptor signaling, but rather to a reduced survival of endogenously secreted insulin on its way to activating the receptor on the cell surface of the target tissues? Here, we present data and lay out arguments in support of this novel hypothesis, which is fundamentally different from the common view that insulin resistance is caused by the body's cells becoming less sensitive to insulin.