Changes

===Aetiology===

===Aetiology===

[[Image:Diabetes Mellitus Type IV hypersensitivity.jpg|right|thumb|150px|Diabetes Mellitus-Brian Catchpole RVC 2008]]

[[Image:Diabetes Mellitus Type IV hypersensitivity.jpg|right|thumb|150px|Diabetes Mellitus-Brian Catchpole RVC 2008]]

Insulin is produced in the beta cells of the pancreatic islets of Langerhans and is released into the circulation to act on specific cell-surface receptors.  Its release is stimulated by rising blood glucose concentration and it is principally insulin which is responsible for the post-prandial gluconeogenesis observed in humans and dogs.  Several hormones (including corticosteroids, progesterone, oestrogen, growth hormone, glucagon and catecholamines) have an antagonistic effect to insulin and cause the blood glucose concentration to increase.  Interruptions at any stage in this pathway may produce the clinical syndrome of diabetes mellitus, including:

[[Insulin]] is produced in the beta cells of the pancreatic islets of Langerhans and is released into the circulation to act on specific cell-surface receptors.  Its release is stimulated by rising blood glucose concentration and it is principally insulin which is responsible for the post-prandial gluconeogenesis observed in humans and dogs.  Several hormones (including corticosteroids, progesterone, oestrogen, growth hormone, glucagon and catecholamines) have an antagonistic effect to insulin and cause the blood glucose concentration to increase.  Interruptions at any stage in this pathway may produce the clinical syndrome of diabetes mellitus, including:

*Failure to produce insulin resulting in an '''absolute deficiency''' - This may be due to [[Pancreas, Endocrine - Degenerative Pathology|degenerative changes in the beta cells]] or it may occur with severe exocrine pancreatic disease that disrupts the islets of Langerhans.  The major example of the latter disease process is [[Pancreatitis|pancreatitis]] and, in cases of this diesase, diabetes mellitus is often found concurrently with [[Exocrine Pancreatic Insufficiency|exocrine pancreatic insufficiency]].  Degeneration of the beta cells, whether it involves the immune system or not, results in '''type 1''' diabetes mellitus and miniature Poodles, Dachshunds and terriers appear to be predisposed to this condition. In humans, it is speculated that immune responses directed at certain pathogens (notably coxsackie virus B1) may cross-react with antigens expressed on the surface of beta cells resulting in immune-mediated destruction of these cells. Whether type 1 diabetes mellitus is associated with a similar misdirected immune response is not yet clear in small animals with several studies giving conflicting results as to the presence of autoantibodies directed at the beta cells at the point at which the disease is first diagnosed.  The pathogenesis would be via [[Type IV Hypersensitivity|Type IV hypersensitivity]]. The CTLs react as if all the beta cells in the pancreas are infected by a virus, as it wrongly detects a self antigen presented by the MHC class I on the surface of the cell as foreign. Autoreactive CD8+ CTLs are inadvertently activated, destroying the beta cells, thus preventing the secretion of insulin and causing diabetes type 1 (see diagram).

*Failure to produce insulin resulting in an '''absolute deficiency''' - This may be due to [[Pancreas, Endocrine - Degenerative Pathology|degenerative changes in the beta cells]] or it may occur with severe exocrine pancreatic disease that disrupts the islets of Langerhans.  The major example of the latter disease process is [[Pancreatitis|pancreatitis]] and, in cases of this diesase, diabetes mellitus is often found concurrently with [[Exocrine Pancreatic Insufficiency|exocrine pancreatic insufficiency]].  Degeneration of the beta cells, whether it involves the immune system or not, results in '''type 1''' diabetes mellitus and miniature Poodles, Dachshunds and terriers appear to be predisposed to this condition. In humans, it is speculated that immune responses directed at certain pathogens (notably coxsackie virus B1) may cross-react with antigens expressed on the surface of beta cells resulting in immune-mediated destruction of these cells. Whether type 1 diabetes mellitus is associated with a similar misdirected immune response is not yet clear in small animals with several studies giving conflicting results as to the presence of autoantibodies directed at the beta cells at the point at which the disease is first diagnosed.  The pathogenesis would be via [[Type IV Hypersensitivity|Type IV hypersensitivity]]. The CTLs react as if all the beta cells in the pancreas are infected by a virus, as it wrongly detects a self antigen presented by the MHC class I on the surface of the cell as foreign. Autoreactive CD8+ CTLs are inadvertently activated, destroying the beta cells, thus preventing the secretion of insulin and causing diabetes type 1 (see diagram).