Characteristics of gastric emptying on glycemic responses in the T2DM-SHR/Ntul//-cp (Corpulent) rat

To determine the characteristics of gastric emptying in lean, obese and obese diabetic rats measures of oral glucose tolerance (OGT) were determined and glycemic parameters of obesity and type II diabetes (T2DM) made. Fasting plasma Insulin, amylin, and markers of insulin resistance were greater in obese than in lean littermates and increased further in both young and old obese+T2DM rats. The oral glucose tolerance and glucose areas under the curve (AUCglc) were modestly impaired in obese LA/Ntul//-cp rats, with only a modest increment in the early phase (0 to +30 min post ingestion) of luminal glucose uptake. The OGT in obese+T2DM rats was markedly impaired, with additional progression in aging. The fractional AUCglc from 0 to+30 minutes was significantly increased in the obese+T2DM rats, and the acceleration in initial glycemic response of OGT was increased 6-fold in young T2DM rats, and remained greatly elevated thereafter. The initial and late post-absorptive glycemic phase of the OGT in old obese was greater than in younger obese T2DM. These results are consistent with epigenetic expression of obesity and obesty+T2DM and with dysregulation in the kinetics of gastric emptying analogous to Dumping Syndrome or Sirt1 dysregulation in the young obese-T2DM phenotype of the SHR/Ntul//-cp rats and the neurologic onset of gastroparesis in old T2DM SHR/Ntul//-cp rats. Thus, the Obese+T2DM rat is a useful model for the further investigation of the pathophysiology of T2DM as it occurs in man and animals.