Glucose tolerance in aging obese (ob/ob) and lean mice.

Examination of the glucose tolerance in younger (3 month) and older (6 month) obese mice revealed that most of their postinjection hyperglycemia arises from the disproportionately large glucose responses to the injection/bleeding procedures rather than from the added glucose. Simultaneous measurements of circulating glucagon, corticosterone and insulin indicated that simple differences in the levels of these hormones, in their circulating ratios, or in the magnitude of the hormone responses to stimulation did not fully account for the "stress"-induced hyperglycemia.

Starvation and age effects on glycoregulation and hormone levels of C57BL/6Job/ob mice.

The contributions of insulin (IRI), glucagon (IRG), and corticosterone production to the glycemic changes associated with age and starvation were examined in 3 and 6 month old ob/ob and lean mice. Three month old ob/ob mice had elevated glucose levels under all feeding conditions, but in older obese mice basal hyperglycemia was evident only after 48 hours of food deprivation. These age differences in glycoregulation were not consistently related to changes of IRI, IRG, or corticosterone concentrations. Similarly, the mild diabetes associated with senescence in lean mice was only evident during food deprivation. This abnormality in glycoregulation was also independent of decreased IRI or elevated diabetogenic hormone concentrations. Our results indicate that there is no simple hormonal basis for the partial remission of diabetes in older ob/ob mice, or for the development of mild diabetes in aging lean mice. Additionally, these data suggest that the tissue 'resistance' that is associated with chronic insulin overproduction might also develop in response to persistent overproduction of other metabolically-active hormones.