Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Endocrine Functions of the Pancreas and Regulation of Carbohydrate Metabolism
Fraction of Secreted Insulin

Insulin and Insulin-like Activity in Blood

In addition to insulin, plasma contains numerous compounds with insulin-like activity (Table 19-2). The activity that is not inhibited by Antibodies is referred to as non-suppressible insulin-like activity (NSILA). This activity persists almost entirely after pancreatectomy and is mediated by Insulin-like Growth Factors IGF-I and IGF-II (see Chapter 22). These growth factors are Polypeptides; small amounts of them circulate in free form in the blood (low-molecular-weight fraction), whereas large amounts are bound to Proteins (high-molecular-weight fraction).

One might wonder why pancreatectomy causes Diabetes Mellitus (see below) if NSILA persists in the plasma. In this regard, it should be noted that the insulin-like activity of IGF-I and IGF-II is low compared to that of insulin.

METABOLISM

The half-life of insulin in human blood is approximately 5 min. The hormone binds to insulin receptors, and a portion of it undergoes internalization (see below).

It is degraded within endosomes formed As a result of endocytosis. The primary enzyme involved in this process is insulin protease, a Cell membrane enzyme that is internalized along with insulin. Notably, Insulin receptors are found in numerous Cells throughout the body, extending beyond the classic insulin-sensitive Tissues where the hormone enhances glucose uptake. In fact, nearly all body tissues are capable of metabolizing some amount of insulin. Nevertheless, under normal conditions, 80% of secreted insulin is degraded in The Liver and Kidneys.