Influence of the mutation "diabetes" on insulin release and islet morphology in mice of different genetic backgrounds.
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 beta cells in the pancreatic islets, irregular islet architecture with intraislet ducts, and degenerative as well as hypertrophic changes in the individual beta 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, db(2J), 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-db(2J)/db(2J) mice were characterized by highly elevated serum insulin levels and only moderate hyperglycemia. Their endocrine pancreas was enlarged and showed an increased proportion of beta cells. Like the islets of normal mice, those of C57BL/6J-db(2J)/db(2J) 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.
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007461:Iodoacetates / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011863:Radioimmunoassay; D013045:Species Specificity; D013194:Staining and Labeling; D013806:Theophylline / Q000494:pharmacology
D001557:Benzenesulfonates; D001786:Blood Glucose; D007328:Insulin; D007461:Iodoacetates; D013806:Theophylline; D005947:Glucose