Multiple roles of insulin

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One way to better understand the link between many risk parameters and elevated risk for type 2 diabetes is to appreciate that insulin imparts its effects on many tissues, not just skeletal muscle and liver but also adipose, endothelium and immune cells (Ritchie etal., 2004; Bloomgarden, 2005; Reaven, 2005). Thus, insulin is relevant not simply to glucose uptake and metabolism, but it also:

• suppresses free fatty acid (FFA) release from adipose tissue;

• limits hepatic triglyceride synthesis;

• helps maintain endothelial homeostasis, with a net vasodilatory effect in insulinsensitive subjects;

• is involved in regulating thrombotic cascades;

• may have a role in regulating inflammatory cascades (Figure 2.3).

It can thus be seen that a partial failure of insulin action, or a resistance to its normal actions at each of these tissues, could lead to a spectrum of metabolic abnormalities that individually and collectively accelerate the atherogenic process. Each of these pathways is now discussed in greater detail. It is important to appreciate that insulin may also have some apparent 'deleterious' actions but that the balance of effects is always protective in insulin-sensitive subjects. This is discussed later on.

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