Estrone treatment dissociates primary versus secondary consequences of "diabetes" (db) gene expression in mice
Estrone treatment dissociates primary versus secondary consequences of "diabetes" (db) gene expression in mice. M Prochazka , F H Premdas , E H Leiter and L G Lipson Abstract Feeding 0.001% estrone in a diet to C57BL/KsJ mice homozygous for the recessive obesity gene "diabetes" (...
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Published in | Diabetes (New York, N.Y.) Vol. 35; no. 6; pp. 725 - 728 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
American Diabetes Association
01.06.1986
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Online Access | Get full text |
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Summary: | Estrone treatment dissociates primary versus secondary consequences of "diabetes" (db) gene expression in mice.
M Prochazka ,
F H Premdas ,
E H Leiter and
L G Lipson
Abstract
Feeding 0.001% estrone in a diet to C57BL/KsJ mice homozygous for the recessive obesity gene "diabetes" (db) permitted dissociation
of the primary consequences of obesity gene expression from the secondary consequences of diabetes effected through interaction
between the db gene and other diabetogenic genes in the inbred background. Estrone-treated db/db mice were similar to untreated
mutants in exhibiting hyperphagia and marked obesity. However, estrone-treated mutants did not develop the hyperinsulinemia,
hyperglycemia, and islet atrophy characteristic of untreated db/db mice. Thus, expression of the primary defect could be studied
in the absence of the myriad secondary sequelae elicited by chronic hyperinsulinemia and hyperglycemia. Reduced numbers of
hepatocyte plasma membrane insulin receptors (50% of normal) persisted in the estrone-treated mice in the absence of hyperinsulinemia,
indicating that this deficiency was a consequence of the primary genetic defect and not merely a downregulation phenomenon
secondary to hyperinsulinemia. Comparison of insulin secretion from comparably sized +/+ islets versus islets from estrone-treated
db/db mice showed no intrinsic defects in beta-cell sensitivity to glucose. In conclusion, db-induced obesity can be dissociated
from hyperinsulinemia, hyperglycemia, beta-cell dysfunction, and hyperphagia but is associated with a generalized membrane
defect reflected in part by the persistent deficiency of plasma membrane insulin receptors. |
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ISSN: | 0012-1797 1939-327X 0012-1797 |
DOI: | 10.2337/diabetes.35.6.725 |