Effects of insulin deficiency

One effect of insulin deficiency is increased breakdown and metabolism of fat for energy. In the absence of insulin, hormone-sensitive lipases are strongly activated, resulting in the release of large quantities of fatty acids and glycerol into the circulating blood.

The combination of insulin lack and fatty acid excess in liver cells result in increasingly active transport of fatty acids into the mitochondria. In the mitochondria, beta-oxidation of fatty acids produces a substantial volume of acetyl-CoA, which is condensed to form acetoacetic acid before being released into the circulating blood.

Typically, the excess acetoacetic acid is converted back to acetyl-CoA by peripheral cells to be used as a source of energy, but insulin deficiency depresses the peripheral utilization of acetyl-CoA. Thus, acetoacetic acid levels simultaneously are increased and under utilized. If insulin lack persists, acetoacetic acid levels may reach dangerous concentrations in the body.

Acetoacetic acid can be converted into beta-hydroxybutyric acid and acetone; together, these three substances are known collectively as ketone bodies. In severe diabetes, build up of ketone bodies can result in the potentially fatal condition, diabetic ketoacidosis.

FIgure $1$‍ demonstrates the effects of insulin lack on the concentrations of blood glucose, circulating fatty acids, and acetoacetic acid.

Figure $1$‍