Glutamic acid decarboxylase is an enzyme that is responsible for synthesizing an important inhibitory neurotransmitter in the body. Research has examined the link between an autoimmune response towards this enzyme and certain diseases. The detection of antibodies against glutamic acid decarboxylase may serve a role in the early detection and treatment of type 1 diabetes 23.
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Glutamic acid decarboxylase (GAD) is the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). GABA is an important inhibitory neurotransmitter in neurons and beta pancreatic cells. The two isoforms in glutamic acid decarboxylase are identified as GAD-67 and GAD-65 2. Both isoforms are present in both the brain and pancreas.
Autoimmunity is the term to describe an attack against native cells and tissues by the immune system. When properly functioning, the immune system protects the body by attacking and eliminating foreign particles such as viruses, bacteria and other harmful substances. The immune system identifies foreign substances by the unique antigens, which are chemical markers located on the surface of these substances. Autoimmunity occurs when the immune system mistakenly identifies native cells and tissues as foreign. The result is an attack on cells and tissues by the immune system. An autoimmune response against glutamic acid decarboxylase in neurons has been implicated in a rare neurological condition known as Stiff-Man syndrome. It has been proposed that a similar autoimmune response against GAD in pancreatic cells may be associated with type 1 diabetes.
Type 1 Diabetes
Diabetes is one of the most prevalent diseases in the Unites States and is a leading cause of heart disease, kidney disease, blindness and amputations. Insulin is a hormone that is normally produced by the pancreas in response to increased levels of glucose in the bloodstream. Levels of blood glucose usually rise after the consumption of food. Insulin initiates transfer of glucose from the bloodstream into cells and tissues for utilization as energy. Type 1 diabetes is a condition where the pancreas is only able to produce minimal amounts of insulin, if any at all. The inability to produce insulin is often due to an autoimmune response that destroys the pancreatic beta cells responsible for synthesizing insulin.
Since glutamic acid decarboxylase is found in pancreatic cells, the presence of antibodies against GAD may suggest that an autoimmune response may occur against pancreatic cells that could lead to the development of type 1 diabetes 3. Although studies have shown a correlation between the presence of GAD antibodies and development of type 1 diabetes, this factor alone is not a definitive predictor of disease. However, it may be a screening tool that can aid in the early identification and treatment of type 1 diabetes.
Additional studies will need to be conducted to determine the strength of correlation between GAD antibodies and development of type 1 diabetes. In addition, the presence of GAD antibodies may become useful in distinguishing between type 1 and type 2 diabetes. As opposed to type 1 diabetes, type 2 diabetes is a condition characterized by an impaired response to insulin rather than the lack of production. In addition, glutamic acid decarboxylase may be found to have a significant role in other cells and tissues as well.
Since glutamic acid decarboxylase is found in pancreatic cells, the presence of antibodies against GAD may suggest that an autoimmune response may occur against pancreatic cells that could lead to the development of type 1 diabetes. The detection of antibodies against glutamic acid decarboxylase may serve a role in the early detection and treatment of type 1 diabetes. The inability to produce insulin is often due to an autoimmune response that destroys the pancreatic beta cells responsible for synthesizing insulin.
- “Journal of Experimental Medicine”; Identification of a Dominant Epitope of Glutamic Acid Decarboxylase (GAD65) Recognized by Autoantibodies in Stiff-Man Syndrome; Butler MH, Solimena M, Dirkx R, Hayday A, De Camilli P.; Dec. 1993
- “American Journal of Epidemiology”; Antibodies to Glutamic Acid Decarboxylase and Diabetes Mellitus in the Multiple Risk Factor Intervention Trial; Zimmet PZ, Shaten BJ, Kuller LH, Rowley MJ, Knowles WJ, Mackay IR; Jul. 1994
- “Clinical Chemistry”; Glutamic Acid Decarboxylase Antibodies in Screening for Autoimmune Diabetes: Influence of Comorbidity, Age, and Sex on Specificity and Threshold Values; Batstra MR, van Driel A, Petersen JS et al; Jan. 1999
- American Diabetes Association: Diabetes Basics
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