Exaggerated pancreatic polypeptide secretion in Pima Indians: Can an increased parasympathetic drive to the pancreas contribute to hyperinsulinemia, obesity, and diabetes in humans?

Vagally-mediated hyperinsulinemia is a common abnormality in various rodent models of genetic and hypothalamic obesity that have a high propensity for type 2 diabetes. We hypothesized that Pima Indians, a population with a hi gh prevalence of hyperinsulinemia, obesity, and type 2 diabetes also have a n increased parasympathetic drive to the pancreas. To test this, we measure d plasma concentrations of insulin and pancreatic polypeptide (PP), a surro gate marker of pancreatic vagal tone, in lean and obese Pima Indian and Cau casian children (n = 43, 26P/17C, 7 +/- 1 y) and adults (n = 92, 61P/31C, 3 1 +/- 5 y). Pima Indian children had similar to2-fold higher fasting insuli n and 57% higher fasting PP concentrations than age- and sex-matched Caucas ian children (P < .05). Although there was no difference in fasting PP conc entration between Pima Indian and Caucasian adults, in response to a mixed meal, Pima Indians had a 51% higher early (30 minutes) PP concentration and 2-fold higher early insulin concentration than Caucasians (P < .05). PP co ncentrations at 60 minutes and 120 minutes after the meal were also markedl y higher in both lean and obese Pima Indians compared with lean and obese C aucasians. These results suggest that Pima Indians may have an increased pa rasympathetic drive to the pancreas, which could lead to a primary hypersec retion of insulin and contribute to their high propensity for obesity and d iabetes, as is the case in various rodent models of obesity. Copyright (C) 2001 by W.B. Saunders Company.