The effect of pertussis toxin on insulin secretion from obese (fa/fa) Zucker rats

The obese (fa/fa) Zucker rat is a genetic model of childhood-onset obesity in humans. Pathological changes seen in this rat include, among others, a pronounced hyperinsulinemia in the presence of normoglycemia. The etiology of elevated blood levels of insulin is unknown. These studies investigated the role of the inhibitory guanine nucleotide binding protein G$\sb{\rm i}$ of adenylate cyclase in the endocrine pancreas. The hypothesis was that function of G$\sb{\rm i}$ in obese rats was compromised, resulting in loss of inhibitory pathways. This loss of inhibition could contribute to hypersecretion of insulin.To test this hypothesis, two separate sets of experiments were performed. Initially isolated pancreatic islets of lean and obese Zucker rats were used. The second experiment employed an isolated perfused pancreas preparation. The function of inhibitory hormones of insulin secretion reported to act via G$\sb{\rm i}$, including epinephrine, somatostatin and galanin, were tested. Pertussis toxin was used to inactivate G$\sb{\rm i}$ both 'in vivo' and in isolated islets. (Abstract shortened by UMI.).Source: Masters Abstracts International, Volume: 30-03, page: 0652