How does hyperglycemia occur?

    Glucose is the primary source of energy for the body. Glucose comes from ingested food and is absorbed in the intestine. It is then metabolized by:
1) Energy production Glycolysis
2) Conversion to amino acids and proteins or keto-acids
3) Storage as glycogen

    Glucose does not always enter the body in the form of glucose however it can be formed from the digestion of dietary carbohydrates. Dietary carbohydrates enter the body in complex forms, such as disaccharides and the polymers starch and glycogen. The polymer cellulose is also consumed but not digested. The first step in the metabolism of digestible carbohydrate is the conversion of the higher polymers to simpler, soluble forms that can be transported across the intestinal wall and delivered to the tissues. The breakdown of polymeric sugars begins in the mouth. Saliva has a slightly acidic pH of approximately 6.8 and contains lingual amylase that begins the digestion of carbohydrates. The action of lingual amylase is limited to the area of the mouth and the esophagus; it is inactivated by the strongly acidic pH of the stomach. Once the food has arrived in the stomach, acid hydrolysis contributes to its further breakdown. Specific gastric proteases and lipases aid in the breakdown process for proteins and fats, respectively. The mixture of gastric secretions, saliva and food is collectively known as chyme and chyme moves onto the small intestine.

    The main polymeric-carbohydrate digesting enzyme of the small intestine is alpha-amylase. This enzyme is secreted by the pancreas and has the same activity as salivary amylase, producing disaccharides and tri-saccharides. The latter are converted to monosaccharides by intestinal saccharides, including maltase, sucrase, and lactase. The net result is the almost complete conversion of digestible carbohydrates to its constituent monosaccharides.

    The resulting glucose and other simple carbohydrates are transported across the intestinal wall to the hepatic portal vein and then to liver cell and other tissues. Nearly all carbohydrates in the diet are converted to glucose following transport to the liver. Catabolism of dietary or cellular proteins generates carbon atoms that can be utilized for glucose synthesis via gluconeogenesis. Additionally, other tissues besides the liver, which incompletely oxidize glucose, can provide lactate that can be converted to glucose via gluconeogenesis. These processes for the production of glucose help to ensure a constant blood glucose level. A constant blood glucose level of approximately 5mM is required to meet the glucose demands of the brain.

    The maintenance of blood glucose levels is of paramount importance to the survival of the human organism. The predominant tissue responding to signals that indicate reduced or elevated blood glucose levels is the liver. The liver can produce glucose at times of low blood sugar levels or it can store glucose at times of elevated blood glucose levels.  Both elevated and reduced levels of blood glucose trigger hormonal responses to initiate pathways to restore glucose homeostasis. Low blood glucose levels trigger the release of glucagon from pancreatic alpha-cells high blood glucose triggers the release of insulin from pancreatic beta cells.

To learn more about insulin click here.

To learn about the insulin receptor click here.

To learn more about glucose transport click here:(this is a medscape file - you must be a registered user to access it; registration is free at: )

    Additional signals, ACTH and growth hormone, released from the pituitary act to increase blood glucose by inhibiting uptake by extra-hepatic tissues. Glucocorticoids also act to increase blood glucose levels by inhibiting glucose uptake. Cortisol, the major glucocorticoid released from the adrenal cortex, is secreted in response to the increase in circulating ACTH. The adrenal medullary hormone, epinephrine, stimulates production of glucose by activating glycogenolysis in response to stressful stimuli.
It is when blood glucose homeostasis fails that diabetes mellitus occurs. If elevated blood glucose levels fail to stimulate the release of insulin from beta-cells or if the insulin released does not function properly then hyperglycemia will persist and the person will have diabetes mellitus.