Control of spontaneous glucose intolerance, hyperinsulinemia, and islet hyperplasia in nonobese C3H.SW male mice by Y-linked locus and adrenal gland.
An inbred strain predisposition to maturity-onset impairment of glucose tolerance was discovered in C3H.SW/SnJ inbred male mice. Males were group-caged from weaning and subjected to repetitive handling stress; deterioration of glucose tolerance developed between 5 and 8 months of age in association with extreme hyperinsulinemia. Some males developed transient chemical diabetes in which plasma glucose concentrations were inappropriately high in relation to the high levels of plasma insulin. By 12 months of age, males previously glucose intolerant had regained a normal glucose tolerance. At death, a massive hypertrophy and hyperplasia of the islet beta-cells was documented in these mice. The impaired glucose tolerance could be circumvented by adrenalectomy at weaning. Although these finding suggested the presence of an obesity gene, the C3H.SW group-caged males were not obese when compared with C3HeB/FeJ males which, although moderately hyperinsulinemic, did not develop the glucose intolerance syndrome. Transfer of the Y chromosome from the C3HeB/FeChp background into the C3H.SW inbred background led to a reduction in the hyperinsulinemic and hyperglycemic stress on the pancreatic islets. Thus the extrinsic environment (caging and handling stress), mediated in part via the adrenal gland, could interact with sex-linked genetic susceptibility modifiers to stimulate hyperplasia of the pancreatic islets and produce a transient insulin resistant state of impaired glucose tolerance in the absence of obesity.
Leiter
E H
EH
Jackson Laboratory, Bar Harbor, Maine 04609.
D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005951:Glucose Tolerance Test; D006965:Hyperplasia; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008820:Mice, Obese / Q000235:genetics*; D012737:Sex Factors; D014998:Y Chromosome
D001786:Blood Glucose; D007328:Insulin