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Diabetes 53:663-671, 2004
© 2004 by the American Diabetes Association, Inc.
Parasympathetic Blockade Attenuates Augmented Pancreatic Polypeptide But Not Insulin Secretion in Pima Indians
1 Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona
2 Ophthalmology Department, Phoenix Indian Medical Center, Phoenix, Arizona
3 Department of Nutrition, University of California-Davis, Davis, California
There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypeptide (PP), an islet hormone considered a surrogate marker of parasympathetic nervous system (PNS) drive to the pancreas. To test if hyperinsulinemia in Pima Indians is due to increased vagal input to the ß-cell, we examined the effect of PNS blockade in 17 Caucasian (aged 35 ± 8 years, body fat 23 ± 7% [mean ± SD]) and 17 Pima Indian males (aged 28 ± 8 years, body fat 29 ± 5%) with normal glucose tolerance. Each participant underwent four consecutive standardized liquid meal tests (64% carbohydrate, 22% fat, and 14% protein) during which a primed infusion of atropine was administered for 120 min at the following doses: 0, 2.5, 5, and 10 µg · kg fat-free mass (FFM)-1 · h-1. Areas under the curve for early (AUC0–30 min) and total (AUC0–120 min) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians (both P = 0.01). Secretion of insulin and PP was inhibited by atropine (both P < 0.001). Increasing doses of atropine attenuated the ethnic difference in PP (P = 0.01) but not in early insulin secretory responses (P = 0.6), an effect that was not due to differences in gastric emptying rate (acetaminophen test) and/or circulating glucose. Similar results were observed for total secretory responses. These results confirm that compared with Caucasians, Pima Indians have an exaggerated PNS drive to pancreatic F-cells that secrete PP. However, the hyperinsulinemia of this population does not appear to be due to increased vagal input to pancreatic ß-cells.
Address correspondence to P. Antonio Tataranni, MD, Clinical Diabetes and Nutrition Section, National Institutes of Health, 4212 N. 16th St., Rm. 5-41, Phoenix, AZ 85016. E-mail: antoniot{at}mail.nih.gov
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