Chronic central nervous system hyperinsulinemia and regulation of arterial pressure and food intake.
OBJECTIVE
Acute studies suggest that insulin has anorexic and hypertensive actions through direct effects on the central nervous system (CNS). However, the importance of these actions in the long-term regulation of food intake and cardiovascular function is still unclear. The goal of the present study was to determine whether chronic increases in CNS levels of insulin, in the absence of changes in plasma insulin concentration, decrease food intake and raise arterial pressure in rats.


METHODS
An intracerebroventricular cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic insulin or vehicle (artificial cerebrospinal fluid, 0.5 mul/h) infusion, via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/day and intravenous infusions. After 4 days of control measurements, insulin (6 mU/h, n = 7 or 12 mU/h, n = 6) or vehicle (n = 4) was infused intracerebroventricularly for 7 days.


RESULTS
Insulin infusion at 6 or 12 mU/h caused transient decreases in food intake, but did not significantly alter plasma glucose or insulin concentrations. Insulin intracerebroventricular infusion also did not alter MAP or HR (106 +/- 2 and 105 +/- 5 versus 104 +/- 2 mmHg in control; 411 +/- 9 and 407 +/- 9 versus 410 +/- 7 bpm in control, respectively). Food intake, MAP and HR remained unchanged in the vehicle-treated group.


CONCLUSIONS
These findings provide no evidence that insulin plays a major role in the long-term regulation of appetite, arterial pressure or HR. However, the CNS actions of insulin may exert modest acute effects on appetite that could play a role in limiting meal size and influencing caloric balance.
Liu
Jiankang
J
Department of Physiology and Biophysics, and Center of Excellence in Cardiovascular Renal Research, The University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
da Silva
Alexandre A
AA
Tallam
Lakshmi S
LS
Hall
John E
JE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006946:Hyperinsulinism / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D007004:Hypoglycemic Agents; D007328:Insulin