Diabetes is a complex metabolic disease that is generally categorized by either relative or absolute insulin deficiency. In 1997 the ADA issued new diagnostic and classification criteria for this disease. The classification of diabetes mellitus includes four clinical classes.
• Type I diabetes (results from beta cell destruction, usually leading to absolute insulin deficiency).
• Type II diabetes (results from a progressive insulin secretory defect on the background of insulin resistance).
• Gestational diabetes mellitus (GDM) usually temporary condition during pregnancy.
• Other types are due to causes ranging from:
a. generic defects in beta cell function
b. genetic defects in insulin action
c. diseases of the exocrine pancreas
d. drug or chemical induction
For the purposes of this report, the concentration will be on type II diabetes. Each type obviously have its own complexities that are unique to it.
Type II diabetes, which is also sometimes known as non-insulin dependent diabetes mellitus (NIDDM) is a “heterogeneous disorder characterized by impaired insulin secretion and reduced tissue sensitivity to insulin” [Rubin]. Within the pancreas, specifically the islets of langerhans exist beta cells. The beta cell is the area where production secretion and sequestering of insulin takes place. The beta cell, which is a sensory cell, contains surface glucose receptors within the plasma membrane, which monitor extraneous cellular glucose concentration. When glucose levels are low insulin is sequestered within the cell in vesicles and production is halted. Simply put when there is less glucose available less enters the beta cell and the metabolism of cell slows. ATP production shows a corresponding decrease. Under these conditions the Ca2+ channels of the beta cell are closed. When glucose levels rise in the extra-cellular environment of the beta cell glucose enters the cell faster and a corresponding increase in ATP production results. The ATP acts as a phosphorilater which leads to the closing of K+ (potassium) channels resulting in cellular depolarization. This leads to Ca++ channels opening as a voltage gating response. Ca++ also has a secondary function that is inducing insulin vesicles to leave the beta cell via exocytosis.
In normal peripheral cells (e.g. adipocyte and skeletal muscle) the binding of insulin to receptors within the plasma membrane of the target cell activates the tyrosine kinase domain instigating intracellular events protein phosphorylation thus leads to an intracellular response that allows glucose to enter via glucose channels.
In a normal person the extra cellular glucose concentration, although variable because of dietary intake and utilization, is exquisitely managed by the opposing actions of insulin and glucagon. (Glucagon is a proteinaceous pancreatic hormone produced by the pancreatic alpha cells that increase the blood sugar). The usual molar ratio of insulin to glucagon in plasma is approximately 2.0. Under conditions requiring endogenous substrates (e.g. glycogen which is the chief animal storage carbohydrate found in the liver and secondarily in skeletal muscle) this ratio may decrease to 0.5 or less, during fasting or exercise. Conversely when substrate storage is advantageous because of dietary in-take ratios may increase to 10. This ratio enhances glucose uptake, oxidation and conversion to liver and muscle glycogen and suppresses proteolysis and lipolysis.
In its most simple explanation insulin and glucagon are associated with glucose metabolism and storage mechanisms however, together they not only coordinate the metabolism of endogenous glucose but also aid digestive processes associated with free fatty acids, amino acids and other substrates to ensure that energy needs are met in the basal state and during exercise. They accomplish the latter via actions consequently imposed
