IMPAIRED GLUCOSE-TOLERANCE IS ASSOCIATED WITH INCREASED ISLET AMYLOID POLYPEPTIDE (IAPP) IMMUNOREACTIVITY IN PANCREATIC BETA-CELLS
- 1 August 1989
- journal article
- research article
- Vol. 135 (2), 245-250
Abstract
Adult cats determined by clinical laboratory evaluations to be normal, impaired glucose tolerant, or overtly diabetic were used to explore prospectively the relationships among pancreatic beta cell islet amyloid polypeptide (IAPP) immunoreactivity, islet amyloid (IA) deposition, and diabetogenesis. IAPP-derived IA was found in 11 of 14 (79%) diabetic cats, in four of nine (44%) impaired glucose tolerant cats, and in two of eight (25%) normal adult cats. The presence of IA even in very small amounts, therefore, predicts a very high probability (88%) that an animal has either impaired glucose tolerance or overt DM. Although all overtly diabetic cats had a marked decrease or absence of beta cell IAPP immunoreactivity, six of six cats with impaired glucose tolerance retained IAPP immunoreactivity with 1:15,000 dilutions of antisynthetic IAPP 7-17, whereas only one of seven normal cats had IAPP immunoreactivity beyond 1:10,000 dilutions. These findings suggest that increased IAPP production preceding the development of ovrert DM is linked to the progressive formation of insoluble IA deposits that are apparent in most overtly diabetic individuals. Of most importance, in that IAPP has been reported to inhibit both basal and insulin-stimulated rates of glycogen synthesis, is the possibility that increased production and release of IAPP by pancreatic beta cells plays a key role in the development of the insulin resistance and impaired glucose tolerance, both of which occur in Type 2 DM.This publication has 21 references indexed in Scilit:
- Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitroNature, 1988
- The pathogenesis of maturity-onset diabetes mellitus: Is there a link to islet amyloid polypeptide?BioEssays, 1988
- Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.Proceedings of the National Academy of Sciences, 1987
- Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.Proceedings of the National Academy of Sciences, 1987
- Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal catsJournal of Comparative Pathology, 1986
- A second human calcitonin/CGRP geneFEBS Letters, 1985
- Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide productsNature, 1982
- The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitusDiabetologia, 1978
- A modification of the unlabeled antibody enzyme method using heterologous antisera for the light microscopic and ultrastructural localization of insulin, glucagon and growth hormone.Journal of Histochemistry & Cytochemistry, 1975
- THE PANCREATIC ISLET CELLS IN INSULAR AMYLOIDOSIS IN HUMAN DIABETIC AND NON‐DIABETIC ADULTSActa Pathologica Microbiologica Scandinavica Section A Pathology, 1973