Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians.
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 beta-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 micro g. kg fat-free mass (FFM)(-1). h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 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 beta-cells.
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
Barbora
B
Vozarova de Courten
Christian
C
Weyer
Norbert
N
Stefan
Mark
M
Horton
Angelo
A
DelParigi
Peter
P
Havel
Clifton
C
Bogardus
P Antonio
PA
Tataranni
D000328:Adult; D001130:Arizona; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D003971:Diastole; D005951:Glucose Tolerance Test; D018737:Hand Strength; D006801:Humans; D007198:Indians, North American; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism*; D013599:Systole; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D044465:White People
D001786:Blood Glucose; D007328:Insulin; D010191:Pancreatic Polypeptide; D001285:Atropine