Effect of drugs interacting with the dopaminergic receptors on glucose levels and insulin release in healthy and type 2 diabetic subjects.
Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and alpha- and beta-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 microg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 microg/kg/min) plus dopamine (0.5-3 microg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30', 60' and 90'): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of beta-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.
Contreras
Freddy
F
Clinical Pharmacology Unit, Vargas Medical School, Central University of Venezuela, Caracas, Venezuela.
Foullioux
Christian
C
Pacheco
Betsy
B
Maroun
Charbel
C
Bolívar
Hector
H
Lares
Mary
M
Leal
Elliuz
E
Cano
Raquel
R
Bermúdez
Valmore
V
Velasco
Manuel
M
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D008875:Middle Aged; D011954:Receptors, Dopamine / Q000187:drug effects*; D013997:Time Factors
D001786:Blood Glucose; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D007328:Insulin; D011954:Receptors, Dopamine; D008787:Metoclopramide; D004298:Dopamine