2-amino-5-iodo-6-phenyl-4-pyrimidinone and Diabetes-Mellitus--Type-2

The islet amyloid polypeptide (IAPP) was originally identified by chemical analysis of the amyloid component in a human pancreatic islet cell tumor. It consists of 37 amino acids and displays about 50% homology with the neuropeptide calcitonin gene-related peptide (CGRP). In the pancreatic islets the IAPP is confined to the beta-cells, co-stored with insulin in the secretory granules and apparently co-secreted with insulin on glucose stimulation. In beta-cell depletion states such as streptozotocin diabetes in animals and in human type I diabetes mellitus both the IAPP and the insulin levels display reduction or are even absent. Within the mature IAPP molecule the amino acid sequence 23-29 shows considerable amino acid heterogenicity among various mammalian species. The amino acid composition of human IAPP in this specific region promotes the development of pancreatic islet amyloidosis, a phenomenon related to the ability to develop type II diabetes in that particular species. However, as type II diabetes is an inherited disease affecting a subpopulation of humans, not only the gene coding mature IAPP, but also one or several other hereditary factors of unknown origin are needed for the disease to develop. We have established a radioimmunoassay for plasma measurements of IAPP. During screening investigations of a large material of endocrine tumors we found a patient with extremely elevated plasma levels of IAPP, about 20,000 pmol/l. Immunohistochemical investigations confirmed the IAPP content and also revealed amyloid deposits. While performing an oral glucose tolerance test insulin levels remained unchanged whereas there was an increase in the glucose and IAPP levels. It is thus concluded that IAPP can be used as a tumor marker in pancreatic islet cell tumors and that high plasma levels of IAPP can inhibit glucose stimulated insulin secretion.

Topics: Animals; Cytosine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Pancreatic Neoplasms; Rats