Glucose Homeostasis Insulin and Glucagon

All cells except brain, active muscle, and liver cells, require membrane transporters for glucose to enter the cells. The transporters are usually present inside the cells and insulin makes them available by bringing them to the cell surface; with dropping insulin levels, they recede again.

Insulin has three major metabolic effects:

1. It lowers blood glucose by:

  • Increasing glucose uptake in various tissues,
  • Inhibiting glycogenolysis,
  • Inhibiting gluconeogenesis.

2. It lowers blood fatty acids and enhances fat storage by:

  • Increasing glucose uptake by fat cells,
  • Activating enzymes that catalyze conversion of glucose into fatty acids,
  • Enhancing fatty acid uptake into fat cells from blood,
  • Inhibiting lipolysis.

3. It lowers amino acid levels in blood and increases protein synthesis by:

  • Increasing amino acid uptake into cells,
  • Increasing amino acid use for protein synthesis,
  • Inhibiting breakdown of proteins.

Insulin secretion by the p-cells of the islets of Langerhans is subject to multiple regulatory mechanisms (A). The most important control value is the blood glucose level, which fluctuates throughout the day. After food intake and before increased blood glucose levels could even trigger this, insulin is released through the function of the autonomic nervous system, and subse quently through food-triggered, gastrointestinal hormones. Glucagon, which is secreted by the a-cells of the islets of Langerhans, is also involved in blood glucose regulation (B). With regards to glucose, glucagon can be considered to be antagonistic to insulin. Their effects on plasma amino acid levels are similar, though. An increase in plasma amino acid levels triggers secretion of insulin as well as glucagon.

The multiple cellular effects of insulin and glucagon are mediated by cell membrane receptors. Binding of gluca-gon to the receptor (C) activates ade-nylate cyclase (1), leading to formation of the second messenger cAMP. cAMP binds to the regulatory subunit of a protein kinase, causing it to release activated catalytic subunits (2). As a result, target enzymes are phosphorylated (3), altering their activity. The insulin receptor (D) is a glycopro-tein consisting of two a- and two p-chains. The latter are membrane-bound and reach into the cytosol. After insulin binds to the a-chains, which are located on the cell's exterior, a part of the p-chains is phosphorylated, forming an active tyrosine kinase. Tyrosine kinase phosphorylates tyrosine R-groups of a peptide (insulin receptor substrate, IRS), which in turn triggers a multiple phosphorylation and dephosphoryla-tion cascade. Dephosphorylation of the receptor finally terminates these intra-cellular effects of insulin.

Glucose Homeostasis 65

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Glucagon And Insulin

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Extracellular Plasma Cytosol space membrane

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