Regulation of blood glucose

Biochemistry Lec. 7 Dr.Thana Alsewedy
Regulation of blood glucose
The maintenance of glucose level in blood within narrow limits is a very important, because it is essential to have continuous supply of glucose to the brain. Glucose homeostasis is regulated by two hormones, insulin (anabolic hormone) and glucagon (catabolic hormone). Low blood glucose triggers release of glucagon from pancreatic ?-cells, High blood glucose triggers release of insulin from pancreatic ?-cells.

The fuel reserves of a healthy adult human are of three
types: glycogen stored in the liver and muscles; triacylglycerol
in adipose tissues; and tissue proteins, which can be degraded when necessary to provide fuel.
Following a meal (fed state or postprandial), glucose is absorbed from the intestine and enters the blood. The rise in the blood glucose level stimulates the secretion of insulin by beta cells of pancreas. Insulin helps in the storage of glucose as glycogen or its conversion to fat.

In Fasting State, the blood glucose level falls after approximately 2-5 hours postprandial. It may go down further; but this is prevented
by hepatic glycogenolysis (glycogen stores are sufficient for about one day in the absence of food intake. In conditions of food deprivation lasting longer than one day a variety of metabolic changes take place) Thereafter, gluconeogenesis will begin. By 24 hours after a meal, blood glucose has fallen further, insulin secretion has slowed, and glucagon secretion has increased. These hormonal signals mobilize triacylglycerols, which now become the primary fuel for muscle and liver. To provide glucose for the brain, the liver degrades certain proteins—those most expendable in an organism not ingesting food (starvation) . Also in the liver, the carbon skeletons of glucogenic amino acids are converted to pyruvate or intermediates of the citric acid cycle. These intermediates, as well as the glycerol derived from triacylglycerols in adipose tissue, provide the starting materials for gluconeogenesis in the liver, yielding glucose for the brain. Eventually the use of citric acid cycle intermediates for gluconeogenesis depletes oxaloacetate, inhibiting entry of acetyl-CoA into the citric acid cycle. Acetyl-CoA produced by fatty acid oxidation now accumulates, favoring the formation of acetoacetyl-CoA and ketone bodies in the liver. After a few days of fasting, the levels of ketone bodies in the blood rise as these fuels are exported from the liver to the heart, skeletal muscle, and brain, which use them instead of glucose. A normal person has fuel reserves to live up
to 45–60 days

In Diabetes mellitus, (caused by a deficiency in the secretion or action of insulin), Individuals with diabetes are unable to take up glucose efficiently from the blood; (recall that insulin triggers the movement of GLUT4 glucose transporters to the plasma membrane of muscle and adipose tissue which take up glucose and in this case insulin deficient) Another characteristic metabolic change in diabetes is excessive but incomplete oxidation of fatty acids in the liver. The acetyl-CoA produced
by oxidation cannot be completely oxidized by the citric acid cycle, because the high [NADH]/[NAD] ratio produced by oxidation inhibits the cycle. Accumulation of acetyl-CoA leads to overproduction of the ketone bodies
ketone bodies
Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketone bodies can be used as fuels, yielding GTP and ATP molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce reducing equivalents (NADH and FADH2), via the citric acid cycle. Ketone bodies cannot be used as fuel by the liver,

Hypoglycemia
Hypoglycemia: Low blood sugar (glucose). Hypoglycemia may be associated with symptoms such as anxiety, sweating, tremor, palpitations, nausea, and pallor. Hypoglycemia also starves the brain of glucose energy, which is essential for proper brain function. Lack of glucose energy to the brain can cause symptoms ranging from headache, mild confusion, abnormal behavior, loss of consciousness, and coma. Severe hypoglycemia can cause death. The causes of hypoglycemia include use of drugs (such as insulin), liver disease, , In some patients, symptoms of hypoglycemia occur during fasting (fasting hypoglycemia). Immediate treatment of severe hypoglycemia consists of administering large amounts of glucose and repeating this treatment at intervals if the symptoms persist.






Map for fed/fast cycle