How blood glucose is regulated?

Blood glucose levels are regulated by the cells of the pancreatic islets (islets of Langerhans). When glucose level is high (e.g. after a meal), beta cells of the islet release insulin into the bloodstream. Insulin stimulates target cells (e.g. muscle cells) to use glucose as energy source. Insulin also induces liver cells to store glucose in the form of glycogen (this process is called glycogenesis). When glucose levels fall (e.g. in the morning before breakfast), another hormone called glucagon is released by alpha cells of the pancreatic islets. Glucagon acts on liver cells to convert glycogen back to glucose and release it into the bloodstream (this process is called glycogenolysis).

How glucose induces insulin release in beta cells?

Shortly after a meal, level of glucose in the blood is up. High glucose level stimulates beta cells to secrete insulin into the bloodstream (Fig. 1 and 2).

Fig. 1: Anatomy of a pancreatic islet (islet of Langerhans): beta cells = blue, alpha cells = red; and an enlarged beta cell (lower panel). Glucose enters beta cell and stimulates exocytosis of vesicles containing insulin. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

Glucose enters beta cell through glucose transporter 2 – GLUT2. Increased intake of glucose => increased production of ATP => ATP/ADP ratio is up => ATP-sensitive potassium channel closed => depolarization of cell membrane => voltage-gated calcium channel opens => increased calcium inside the cell => insulin granule exocytosis.

Fig. 2: Chain of events that lead to secretion of insulin from beta cells. See text for details. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

How insulin induces glucose uptake in target cells?

Insulin and glucose travel in bloodstream to reach target organs (e.g. muscles, liver,..). In target organs, insulin induces cells to take up glucose. Insulin binds to insulin receptor on target cell => phosphorylation of cytoplasmic domain of receptor => a cascade of signaling events brings the GLUT4 (glucose transporter 4) to the membrane of the cell => glucose enters target cell through GLUT4.

Fig. 3: Insulin signaling in target cell. See text fior details. Click on image to see a larger version on Alila Medical Media website where the image is also available for licensing.

Glucagon

Glucagon is secreted into the bloodstream in response to hypoglycemia – low blood sugar. Glucagon has the opposite effect of insulin, its action increases blood glucose level. Glucagon secretion from alpha cells is suppressed by high level of glucose. Low concentration of glucose => increase level of glucagon. Glucagon stimulates breakdown of glucogen stored in liver cells (hepatocytes) and release of glucose into the blood.