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Diabetes in Pets

Amyloidosis

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Amyloidosis is a major cause of diabetes, and is also one of the major forms of damage done to the pancreas by high blood sugar. Diabetic cats may still have a workable pancreas, but if left at high blood sugar levels over time, irreversible damage may be caused to the pancreas, which will continually reduce chances of remission. Amyloidosis from other causes can attack a healthy pancreas causing diabetes, too.

Pancreatic damage is caused by a combination of glucose toxicity and amyloidosis from high blood sugar, such that the insulin-producing Islets of Langerhans[1] of the pancreas become clogged with amyloid deposits. 80-95% of diabetic cats present with type-2 (insulin-resistant) diabetes[2], and it is probably these type-2 diabetic cats who are candidates for remission, but hyperglycemia, left untreated, may damage the pancreas over time, making remission impossible. Diabetic dogs are almost invariably type-1 and so do not usually have remission.

Like diabetes itself, amyloidosis[3], can cause gastroparesis.

Dogs are not known to develop islet amyloids, however this process can occur in canines in connection with insulinomas[4](pancreatic tumors causing the pancreas to produce too much insulin)[5].


MechanismEdit

Amyloidosis is a disorder of protein folding[6][7]. When proteins are not completely or properly folded, they become insoluble (not able to be dissolved). These proteins form fibrils[8], which are fiber-or filament like and interfere with tissue function.

The buildup of amyloid proteins can occur in any organ, and can happen for many reasons, some of which are not known[9].

The amyloid deposits formed in organs cause them to become enlarged; a liver enlarged because of amyloids is referred to as hepatomegaly (The "megaly" medical suffix means enlargement.). Amyloidosis in the pancreas can cause diabetes, and diabetes can also cause amyloidosis in the pancreas. Here's how:

Amylin[10] (also known as islet amyloid polypeptide or IAPP) is a protein normally produced in the beta cells of the pancreas along with insulin, as a response to high blood sugar.

The high blood sugar temporarily suppresses beta cell insulin production, (a vicious circle of its own), so that little insulin is made, but amylin continues to be produced. Lack of insulin leads to further hyperglycemia which stimulates higher amylin production, some of which remains lining the islets.

Oxidization caused by glucose toxicity denatures[11] (disrupts the proper folding of) the amylin (as well as some vital proteins in the islets), which congeals and thickens the deposited amylin into amyloid, which clogs the islets more effectively.

Once the islets are blocked, insulin production is blocked and the beta cells which produce it die[12]. When this happens to most of the pancreas, remission is no longer possible.

At present, it is believed that cats process IAPP differently[13],--thus it continues building up and being turned into amyloid. Age is also a factor, with older cats having amyloids in a larger percentage of their islet cells.

Comparing diabetic and non-diabetic cats of the same age shows that those with diabetes have more amyloid-affected islet cells than those without diabetes.

Medication warningsEdit

Warning: Glipizide and similar oral diabetic medicines have been shown to increase amyloid production and, in the presence of hyperglycemia, amyloidosis, and therefore to damage the pancreas, as reported in this academic study[14] See also Hoenig M, O’Brien TD (1998) Glipizide leads to amyloidosis in a cat model of type 2 diabetes (Abstract). Diabetologia (Suppl. 1), A648

Warning: Using steroids in an amyloidosis patient accelerates the buildup of amyloid deposits; they are not to be used in these patients[15].

Further ReadingEdit

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ReferencesEdit

  1. Wikipedia:Islets of Langerhans
  2. Understanding Feline Diabetes Mellitus, Dr. J Rand, Dr. R Marshall
  3. Amyloidosis and Gastroparesis
  4. Medline-Insulinoma
  5. Canine IAPP cDNA Sequence Provides Important Clues Regarding Diabetogenesis and Amyloidogenesis in Type 2 Diabetes Biochemical & Biophysical Research Communications-1990
  6. Amyloidosis: A Model of Misfolded Protein Disorder-Medecine Sciences-2005
  7. Protein Folding & its Links With Human Disease-Biochemical Society Symposium-2001
  8. Dorlands Medical Dictionary-Fibril
  9. Amyloidosis: New Strategies for Treatment International Journal-Biochemistry & Cell Biology-2003
  10. Wikipedia:Amylin
  11. Wikipedia:Protein Denaturation
  12. Role of Islet Amyloid in Type 2 Diabetes-International Journal of Biochemistry & Cell Biology-2006
  13. Feline Amyloid Deposits
  14. Oral Medications, Hyperglycemia & Amyloid Production.
  15. Amyloidosis-Provet UK
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