Chapter: Modern Pharmacology with Clinical Applications: Insulin and Oral Drugs for Diabetes Mellitus

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Glucose Homeostasis

Carbohydrates, particularly glucose, are an important source of fuel for living organisms.

GLUCOSE HOMEOSTASIS

 

Carbohydrates, particularly glucose, are an important source of fuel for living organisms. Glucose is a major energy source for all cells, and some tissues (e.g., brain) need a continuous delivery of glucose. Maintenance of serum glucose concentrations within a normal physio-logical range, critical to the maintenance of normal fuel use, is primarily accomplished by two pancreatic hor-mones, insulin and glucagon. Derangements of gluca-gon or insulin regulation can result in hyperglycemia or hypoglycemia, respectively.

 

Glucose penetrates most tissues slowly unless in-sulin is present to facilitate its uptake; however, central nervous system (CNS) cells, capillary endothelial cells, gastrointestinal epithelial cells, pancreatic cells, and re-nal medullary cells are freely permeable to glucose.

 

The endocrine portion of the pancreas, called the islets of Langerhans, consists of cordlike groups of cells arranged along pancreatic capillary channels. Two ma-jor types of secretory cells exist within the islets: β-cells, which produce glucagon; and β-cells, which produce in-sulin. Other cell types are also present in the islets, in-cluding the β-cells, which secrete somatostatin, and PP cells, which produce pancreatic polypeptide. These pancreatic cells monitor changes in the availability of small calorigenic molecules, namely glucose, and to a lesser extent amino acids, ketone bodies, and fatty acids. Pancreatic β-cells appropriately alter their rates of insulin secretion in response to fluctuations in the levels of these calorigenic molecules, with glucose playing the dominant role in regulation of insulin secre-tion. Pancreatic β-cells secrete glucagon in response to increases in amino acid and fatty acid levels; how-ever, glucose inhibits glucagon secretion. If blood glucose levels fall (e.g., during hypoglycemia or fast-ing), glucagon secretion is augmented, providing a counterregulatory hormonal response that stimulates gluconeogenesis in the liver and other tissues to avoid hypoglycemia.

 

Blood glucose concentrations are strictly main-tained within homeostatic limits by a variety of bio-chemical and physiological control mechanisms. Circulating glucose levels are determined by the bal-ance among absorption, storage, production, and use (metabolic rate). Glucagon and insulin are the two most important hormones that maintain glucose homeostasis when blood concentrations are perturbed.

 

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