Adrenalectomy improves glycemic responses in congenic obese LA/Ntul//-cp RATS

Abstract

To determine the effects of adrenalectomy on typical insulin-mediated glycemic responses in male obese rats, groups (n=6 -12 rats/phenotype) of normally reared congenic lean and obese animals were fed a Purina chow diet from 6 to 9 weeks of age, and the Chow diet plus a highly palatable cafeteria diet from 9 to 12 weeks of age. The congenic LA/Ntul//-cp rat strain is noted for its longevity and early expression of the obese trait but remains non-diabetic throughout much if not all of its normal lifespan. Subgroups of obese animals were subjected to bilateral adrenalectomy (ADX) at 6 weeks of age to remove glucocorticoid contributions to glycemic parameters. Measures of weight gain (WG )and of glucose tolerance (OGT) were obtained in the three treatment groups at 6, 9 and 12 weeks of age. WG on ADX-obese rats was similar to that of their lean littermates at 6 and 9 weeks of age on the chow diet but increased to twice that observed in their lean littermates from 9 to 12 weeks of age. OGT responses after 30 to 60 minutes and the area under the OGT curve were impaired but not diabetic in obese animals at all ages compared to lean littermates and returned toward those of normally lean rats after ADX. The Insulin to glucose ratio (I:G) was also consistent with insulin resistance in obese but not in ADX-obese or lean rats at 12 weeks of age. In conclusion, ADX resulted in normalization of OGT and glycemic parameters in the obese phenotype at 9 and 12 weeks of age. These results are consistent with normalization of typical insulin-mediated components of glycemic parameters and glucose uptake in peripheral tissues following adrenalectomy of congenic obese rats. The results further suggest that the counterregulatory effects of insulin and glucocorticoid hormones may be contributory to the impaired glycemic responses in the obese phenotype of the LA/N//-cp (corpulent) rat and are consistent with a receptor-mediated element in the development of insulin resistance and glucose uptake in peripheral tissues commonly associated with the early development of obesity in this strain.