Isolated amyloidosis of the pancreatic islets

Isolated pancreatic islet amyloidosis is one of the most common and well-studied forms of endocrine amyloidosis (APUD amyloidosis). It is detected in insulin-producing tumors and in more than 90% of patients with non-insulin-dependent diabetes only, and more often in elderly people. Therefore, isolated pancreatic islet amyloidosis is also one of the forms of senile local amyloidosis, occurring among the latter in 24.5% of cases.

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Causes and pathogenesis of pancreatic islet amyloidosis

It should be borne in mind that isolated amyloidosis of the pancreatic islets is not the only manifestation of pancreatic lesions in amyloidosis. Its vessels are affected in all systemic (generalized) forms: AL (primary amyloidosis), AA (secondary amyloidosis), FAP (hereditary amyloidosis, familial amyloid neuropathy), ASCi (systemic senile amyloidosis). In these forms, arteries of various calibers are mainly involved. In the overwhelming majority of cases, these lesions do not lead to dysfunction of the pancreas. In cases where amyloidosis of the arteries, especially small ones, is severe, atrophy and lipomatosis of the pancreas with dysfunction of its exocrine function are possible. In isolated amyloidosis of the pancreatic islets, we are talking about the loss of the endocrine function of the gland.

The study of isolated amyloidosis of pancreatic islets began with the works of E. L Opie. In 1901, he described the replacement of pancreatic islets by a homogeneous substance in a patient with diabetes mellitus, which he mistakenly considered to be hyaline. Forty years later, N. Gellerstedt proved the amyloid nature of these changes. In 1970, P. Lacy included isolated amyloidosis of pancreatic islets in the group of senile amyloidosis.

Most researchers recognize the decisive role of B cells in the formation of islet amyloid. Until recently, islet amyloid was considered to be a derivative of insulin or insulin beta chains. In 1986-1987, islet amyloid peptide was isolated in pure form from insulinoma amyloid, and then from islet amyloid in insulin-independent diabetes. Biochemical analysis showed that the peptide consists of 37 amino acids, and in terms of amino acid sequence, it is 46% identical to the human neuropeptide: calcitonin-related peptide-2 (CGRP-2) and CGRP-1 (the names of the peptides indicate that they are the product of the same gene as calcitonin). After it was established that islet amyloid peptide has hormonal activity and is contained in the islet apparatus not only in insulin-independent diabetes but also in the norm, it was renamed amylin. The amylin gene in humans is found on chromosome 12 (the insulin gene is on chromosome 11) and has an evolutionary commonality with the CGRP-1 and CGRP-2 genes.

Immunohistochemically, amylin is detected in islet B cells in the same secretory granules as insulin, and is present in fairly large quantities in the blood of patients with insulin-independent diabetes. A correlation is found between the active mass of B cells and the ability to secrete amylin under the influence of pharmacological agents. In elderly and senile individuals, amyloid formation in pancreatic islets is probably associated with a high local concentration of amylin, rather than with damage to its primary structure.

Amyloid of pancreatic islets has some peculiarities: it does not contain tyrosine and tryptophan, does not react with serums to fibrillar proteins of amyloid (AA, AL, ASGi, FAP), but its plasma component is the same as in other types of amyloid. Under electron microscopy, amyloid fibrils are found in close contact with B-cells on their cytomembrane or intracellularly.

The degree of isolated amyloidosis of the pancreatic islets varies widely - from minimal deposits in the form of small plaques along the capillaries, more often along the periphery of the pancreatic islets, to severe amyloidosis, when almost all of the islet tissue is replaced.

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Symptoms of pancreatic islet amyloidosis

Symptoms of isolated pancreatic islet amyloidosis are typical: approximately 70% of patients develop insulin-independent diabetes mellitus, and the severity of diabetes depends on the degree of pancreatic islet amyloidosis, which is confirmed by morphometric examination. In this regard, the discussion of the relationship between diabetes mellitus and isolated pancreatic islet amyloidosis (what is primary and what is secondary) can be considered complete - we are not talking about diabetic pancreatic islet amyloidosis, but about amyloid diabetes. The diagnosis of isolated pancreatic islet amyloidosis is, unfortunately, posthumous, although the achievements of modern medical instrumentation and molecular biology could make it intravital.

Isolated amyloidosis of the pancreatic islets deserves special attention as an age-related problem. It should be confirmed that senile diabetes is amyloid diabetes. The validity of this statement is evidenced by the fact that after 60 years, as we age, the frequency of isolated amyloidosis of the pancreatic islets increases, reaching a peak after 80 years, especially in women. Clinical manifestations of diabetes occur in 66.6% of cases. Therefore, isolated amyloidosis of the pancreatic islets becomes one of the components of the Schwartz tetrad as a manifestation of polyorgan senile amyloidosis - the heart, blood vessels, pancreatic islets and brain. However, the Schwartz tetrad is quite rare (in 5.5% of autopsies of elderly and senile individuals). Significantly more often, isolated amyloidosis of the pancreatic islets is combined either with isolated amyloidosis of the atria and senile amyloidosis of the aorta, or with senile cerebral amyloidosis and senile amyloidosis of the eye.

Thus, isolated amyloidosis of the pancreatic islets in the overwhelming majority of cases is a geriatric and gerontological problem.