Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians

Diabetes. 2004 Mar;53(3):663-71. doi: 10.2337/diabetes.53.3.663.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Arizona
  • Atropine / pharmacology
  • Blood Glucose / metabolism
  • Body Constitution
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diastole
  • Glucose Tolerance Test
  • Hand Strength
  • Humans
  • Indians, North American
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Pancreatic Polypeptide / blood
  • Pancreatic Polypeptide / metabolism*
  • Systole
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*
  • White People

Substances

  • Blood Glucose
  • Insulin
  • Pancreatic Polypeptide
  • Atropine