Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians
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Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians. / de Courten, Barbora; Weyer, Christian; Stefan, Norbert; Horton, Mark; DelParigi, Angelo; Havel, Peter; Bogardus, Clifton; Tataranni, P Antonio.
In: Diabetes, Vol. 53, No. 3, 01.03.2004, p. 663-71.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians
AU - de Courten, Barbora
AU - Weyer, Christian
AU - Stefan, Norbert
AU - Horton, Mark
AU - DelParigi, Angelo
AU - Havel, Peter
AU - Bogardus, Clifton
AU - Tataranni, P Antonio
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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.
AB - 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.
KW - Adult
KW - Arizona
KW - Atropine
KW - Blood Glucose
KW - Body Constitution
KW - Diabetes Mellitus, Type 2
KW - Diastole
KW - European Continental Ancestry Group
KW - Glucose Tolerance Test
KW - Hand Strength
KW - Humans
KW - Indians, North American
KW - Insulin
KW - Pancreatic Polypeptide
KW - Systole
KW - Vagus Nerve
M3 - Journal article
C2 - 14988250
VL - 53
SP - 663
EP - 671
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -
ID: 33926391