Islet amyloid polypeptide (amylin) and insulin are differentially expressed in chronic diabetes induced by streptozotocin in rats.
Islet amyloid polypeptide (IAPP) is overexpressed relative to insulin under several experimental conditions relevant to diabetes mellitus, including the immediate phase (7 days) following induction of streptozotocin diabetes. In the present study, IAPP and insulin gene expression were examined in chronic streptozotocin diabetes (3 weeks) in rats. Quantitative in situ hybridization, determining grain areas and optical densities of mRNA labelling, revealed that IAPP and insulin expression were reduced at the islet level at both low and high streptozotocin doses, partly due to reduced beta-cell mass. In contrast, the cellular levels of IAPP mRNA were either increased or unaffected at the low and high streptozotocin doses, respectively, whereas those of insulin mRNA were unaffected or reduced. When dexamethasone was administered to rats given the low streptozotocin dose, IAPP expression was increased, whereas that of insulin was markedly reduced. Immunocytochemistry revealed that IAPP predominantly occurred in insulin cells and to a lesser extent in somatostatin cells at all treatments examined. Our findings demonstrate that IAPP and insulin gene expression are differentially regulated; the over-expression of IAPP relative to insulin is augmented when the beta-cell insult is aggravated, in our experiments represented by massive beta-cell destruction (high streptozotocin dose) or a combination of moderate beta-cell damage and peripheral insulin resistance (low streptozotocin dose and dexamethasone). An over-expression of IAPP relative to insulin may therefore be involved in diabetes pathogenesis, contributing to its metabolic perturbations, possibly through the capacity of IAPP to restrain insulin release and action and to form islet amyloid.
Mulder
H
H
Department of Physiology and Neuroscience, University of Lund, Sweden.
Ahrén
B
B
Sundler
F
F
D000682:Amyloid / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006168:Guinea Pigs; D017403:In Situ Hybridization / Q000379:methods; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000166:cytology; D011384:Proinsulin / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D011877:Radionuclide Imaging; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D013311:Streptozocin
D000682:Amyloid; D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D013004:Somatostatin; D013311:Streptozocin; D003907:Dexamethasone; D011384:Proinsulin