Effect of Drugs Interacting With the Dopaminergic Receptors on Glucose Levels and Insulin Release in Healthy and Type 2 Diabetic Subjects

Abstract

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.

Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion

“…Such enhanced mixing of luminal contents with the mucosa is likely to have occurred over relatively short distances, since there was no increase in flow events that could be detected by impedance. Exogenous dopamine has been consistently demonstrated to increase insulin secretion (5,23,24). However, the effect of the dopamine antagonist metoclopramide on insulin secretion is less consistent.…”

Effect of Cabergoline on Metabolism in Prolactinomas

“…Although studies evaluating the effects of dopamine agonists on lipid metabolism are not fully consistent, several investigations have demonstrated the improvement in lipid profile after treatment with either BRC or CAB in patients with prolactinomas, regardless of changes in body weight and BMI [42,45,48]. Conversely, a few studies [30,70] failed to demonstrate dopamine and/or dopaminergic drugs to induce a significant change in lipid profile in either healthy or diabetic subjects. This difference could be explained taking into consideration the heterogeneity of administered treatments as well as the small size of patient populations and the short-term treatment with dopamine.…”

Increase of PPARδ by dopamine mediated via DA-1 receptor-linked phospholipase C pathway in neonatal rat cardiomyocytes

“…In order to know the main receptor involved in dopamine-induced actions, we used SCH23390 at concentration sufficient to block DA 1 receptors (Ding et al, 2008), metoclopramide as an effective antagonist of DA 2 receptors (Contreras et al, 2008(Contreras et al, , 2010 and propranolol for the blockade of β-adrenergic receptors (Schaeffer et al, 2004). Actions of dopamine regarding the increase of PPARδ expression and cTnI phosphorylation were both inhibited by 0.1 μmol/L of SCH23390 ( Fig.…”