Regulation of blood glucose concentration
The exocrine pancreas (and other tissues) is primed to expect a rise in blood glucose concentration by peptide hormones such as gastric inhibitory peptide (GIP) that are secreted from enteroendocrine cells within the mucosa of the small bowel. As the glucose concentration in blood rises above 5 mM after a meal, these peptide hormones amplify the response of the β-cells of the endocrine pancreas, resulting in the dis-charge of the hormone insulin from secretory gran-ules which fuse with the cell membrane. Insulin has several effects on metabolism, including facilitating the transport, by GLUT4, of glucose into adipocytes and muscle cells.
In healthy people, blood glucose concentration (glycemia) is homeostatically controlled within a fairly narrow range. It seldom falls below about 5 mM, even after a prolonged fast, and returns to this value within a couple of hours of a meal. In the absence of uptake from the gut (the postabsorptive state), about 8 g glucose per hour is provided for those tissues with an obligatory demand for glucose – namely, the brain, red blood cells, mammary gland, and testis – by breakdown of stores of glycogen in the liver and muscle and by gluconeogenesis. The brain of an adult has a glucose requirement of about 120 g/day. The amount readily available in glycogen approximates 190 g. In long periods of fasting and starvation glucose must be formed from noncarbohydrate sources by a process known as gluconeogenesis. Gluconeogenesis occurs in the liver (responsible for about 90% of gluconeogenesis) and kidney and is the synthesis of glucose from a range of substrates including pyruvate, lactate, glycerol, and amino acids. Amino acids are derived by catabolism of the body’s proteins. All amino acids, with the exceptions of lysine and leucine, are glucogenic. Triacylglycerols (from adipose tissue) are catabolized to release glycerol. These gluconeo-genic processes are triggered by a fall in blood glucose concentration below about 5 mM and are signaled to the tissues by the secretion of glucagon and the glu-cocorticoid hormones.