Influence of the mutation "diabetes" on insulin release and islet morphology in mice of different genetic backgrounds |
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| Authors: | L Boquist B Hellman Lernmark and I-B Tljedal |
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| Affiliation: | From the Departments of Pathology and Histology, University of Umeå, Umeå, Sweden |
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| Abstract: | Mice, 7–8-mo old, of the C57BL/KsJ-db strain and homozygotic for the mutant gene db, exhibited marked hyperglycemia and moderately elevated serum insulin levels. Light and electron microscopy provided evidence of a slightly decreased proportion of β cells in the pancreatic islets, irregular islet architecture with intraislet ducts, and degenerative as well as hypertrophic changes in the individual β cells. As a rule, islets microdissected from these mice did not release insulin in response to glucose, theophylline, iodoacetamide, or chloromercuribenzene-p-sulphonic acid. The absence of secretory responses was not simply due to lack of insulin. Although the islet content of insulin was decreased in C57BL/KsJ-db/db mice, the remaining amount was severalfold larger than that released from stimulated islets of normal controls. Another mutation, db2J, an allele of db with identical phenotypic expressions in the C57BL/KsJ strain, was studied on the genetic background C57BL/6J. In contrast to the severely diabetic C57BL/KsJ-db/db animals, the C57BL/6J-db2J/db2J mice were characterized by highly elevated serum insulin levels and only moderate hyperglycemia. Their endocrine pancreas was enlarged and showed an increased proportion of β cells. Like the islets of normal mice, those of C57BL/6J-db2J/db2J mice responded to glucose and chloromercuribenzene-p-sulphonic acid, the glucose-induced responses being potentiated by theophylline or iodoacetamide. C57BL/KsJ-db/db mice should provide a valuable model for studying defects in insulin secretion in relation to diabetes mellitus. Mice of the C57BL/6J strain offer a control material that may help to elucidate the dependence of the insulin secretory defect on the background genome. |
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