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Islet amyloid polypeptide is a novel 37 amino-acid-residues polypeptide which has been isolated from amyloid deposits in an insulinoma, and in human and cat islets of Langerhans. The molecule has 46% homology with the calcitonin gene-related peptide. Light microscopy examination of the pancreas shows that islet amyloid polypeptide immunoreactivity is restricted to the islet B cells. The present study utilized a rabbit antiserum against a synthetic peptide corresponding to positions 20-29 of islet amyloid polypeptide, a sequence without any amino-acid identity with calcitonin gene-related peptide. By applying the immunogold technique at the ultrastructural level, it was shown that both insulin and islet amyloid polypeptide immunoreactivity occurs in the central granular core of the human B cell secretory granules, while the A cells remain unlabelled. The demonstration that islet amyloid polypeptide is a granular protein of the B cells may indicate that it is released together with insulin. Further studies are necessary to evaluate the functional role of islet amyloid polypeptide. [ABSTRACT FROM AUTHOR]

A novel peptide, islet amyloid polypeptide (IAPP), with structural resemblance to calcitonin gene-related peptide has recently been purified from amyloid deposits in an insulinoma and from islets of Langerhans. By immunohistochemical methods, using antisera to a synthetic undecapeptide of IAPP and to insulin, we show that freshly fixed islet B cells in man, guinea pig, rat, mouse and hamster exhibit strong IAPP-immunoreactivity while A cells are unreactive. In human autopsy material, all of 11 non-diabetic individuals had IAPP immunoreactivity of the islets. In comparison 8 of the 13 patients with Type 2 (non-insulin-dependent) diabetes had no IAPP immunoreactive cells. The proportion of islet cells having IAPP immunoreactivity exceeded 10% in only 1 of the 5 remaining diabetic patients while in all 13 patients substantially more than 10% of the islet cells contained immunoreactive insulin. IAPP-positive amyloid deposits were found in 20-99% of the islets in 12 of the Type 2 diabetic patients while 6 of 11 non-diabetic subjects had amyloid in 3-11% of their islets. In islets with IAPP-immunoreactive amyloid, very few IAPP-cells were seen despite a strong reaction of the B cells with antiserum to insulin. This study shows that IAPP is a normal islet B cell component and that IAPP immunoreactivity in B cells is diminished in Type 2 diabetes while IAPP is deposited as amyloid fibrils in the islets of Langerhans. Although the function of IAPP is unknown, its occurrence in the islet B cells and its structural relation to calcitonin gene-related peptide makes a hormonal nature probable. The present study indicates an altered expression or metabolic fate of IAPP in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Amyloid deposition is the most typical islet alteration in Type 2 (non-insulin-dependent) diabetes. In the present study we show by immunohistochemistry that the amyloid reacts with an antiserum against insulin B chain. Islet amyloid was also purified, dissolved in guanidine-HCl and gel filtered on a Sepharose 6B column. Immunization of a guinea pig with a high molecular weight fraction from this gel filtration resulted in an antiserum with insulin-binding capacity. This binding was partially blocked with pure insulin B chain. The results indicate that islet amyloid contains insulin B chain and that the amyloid is a product of the islet B cells. Thus the study support previous morphological studies. [ABSTRACT FROM AUTHOR]

Pancreatic islet volumes of patients with and without maturity onset diabetes mellitus were estimated. The islet volume of the diabetic patients was 1.01±0.12 cm (SEM) and that of the nondiabetic patients 1.60±0.16 cm with considerable overlap between the two groups. Islet amyloidosis was found in all the diabetic and in 9 of the 15 nondiabetic patients. When the amyloid deposits were excluded, the islet volume of the diabetic patients was 0.89±0.10 cm, while that of the non-diabetic patients was unchanged, 1.60±0.16 cm. There was still some overlapping. Since amyloid deposits seem to destroy the B cell membranes, it was postulated that a comparison of the volumes of islets completely free of amyloid might give a more true picture of the quantitative islet alterations in maturity onset diabetes. It was found that this islet volume of the diabetics was only 0.41±0.05 cm and that of the nondiabetic patients 1.58±0.16 cm. These values correspond better to the altered insulin secretion in maturity-onset diabetes mellitus. [ABSTRACT FROM AUTHOR]