Amyloidosis

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 of the pancreas become clogged with amyloid deposits. 80-95% of diabetic cats present with type-2 (insulin-resistant) diabetes, 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, can cause gastroparesis.

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

Mechanism

Amyloidosis is a disorder of protein folding. When proteins are not completely or properly folded, they become insoluble (not able to be dissolved). These proteins form fibrils, 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.

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 (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 (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. When this happens to most of the pancreas, remission is no longer possible.

At present, it is believed that cats process IAPP differently,--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 warnings

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 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.

Further Reading

• Experimentally induced islet amyloidosis in cats, by U of Georgia
• Feline Insular Amyloid and Insulin-Related Protein
• Feline Insular Amyloid:Association With Diabetes Mellitus-Veterinary Pathology-1981
• Pathogenesis of Feline Diabetes-Molecular & Cellular Endocrinology-2002
• Structure of Cat Islet Amyloid Polypeptide and Identification of Amino Acid Residues of Potential Significance for Islet Amyloid Formation-Diabetes-1990
• Feline Models of Type 2 Diabetes Mellitus-ILAR Journal-National Research Council-2006
• Feline Insular Amyloid-Incidence in Adult Cats With No Evidence of Diabetes Mellitus-Veterinary Pathology 1981

• Amyloidosis in general
• Islet Amyloid-A culprit in Type-II diabetes
• How glucose damages beta cells, by PNRI (See beta cells here.)
• Islet Amyloid and Natural Progression of Type-2 Diabetes (from pdf), JOP, Dr. M. Hayden
• Amyloidosis--General Overview
• Banting Lecture 1990. Beta-cells in Type II Diabetes Mellitus--Diabetes 1991
• Islet Amyloid Polypeptide: a Review of its Biology andPotential Roles in the Pathogenesis of Diabetes Mellitus-Veterinary Pathology-1993
• Islet Amyloid Polypeptide: Mechanisms of Amyloidogenesis in the Pancreatic Islets and Potential Roles in Diabetes Mellitus-Laboratory Investigation-1992.
• Conservation of the Sequence of Islet Amyloid Polypeptide in Five Mammals is Consistent With its Putative Role as an Islet Hormone-Proceedings-National Academy of Sciences-US-1989
• Sequence Divergence in a Specific Region of Islet Amyloid Polypeptide (IAPP) Explains Differences in Islet Amyloid Formation Between Species-FEBS Letters-1989
• Islet Amyloid Polypeptide: Pinpointing Amino Acid Residues Linked to Amyloid Fibril Formation-Proceedings-National Academy of Sciences-US-1990
• "A" is for Amylin and Amyloid in Type 2 Diabetes Mellitus Drs. Hayden & Tyagi-Journal of the Pancreas 2001
  Excellent article with illustrative images explaining amyloid formation process.