Insulin and Oral Drugs for Diabetes Mellitus

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 physiological range, critical to the maintenance of normal fuel use, is primarily accomplished by two pancreatic hormones, insulin and glucagon. Derangements of glucagon or insulin regulation can result in hyperglycemia or hypoglycemia, respectively. Glucose penetrates most tissues slowly unless insulin is present to facilitate its uptake; however, central nervous system (CNS) cells, capillary endothelial cells, gastrointestinal epithelial cells, pancreatic cells, and renal 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 major types of secretory cells exist within the islets: -cells, which produce glucagon; and -cells, which produce insulin. Other cell types are also present in the islets, including the -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 -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 secretion. Pancreatic -cells secrete glucagon in response to increases in amino acid and fatty acid levels; however, glucose inhibits glucagon secretion. If blood glucose levels fall (e.g., during hypoglycemia or fasting), glucagon secretion is augmented, providing a counterregulatory hormonal response that stimulates D R U G L I S T Insulin and Oral Drugs for Diabetes Mellitus