Background and objective

The importance of the brain as a regulator in glucose homeostasis is emerging. Central dopaminergic activity follows a circadian rhythm with a surge in the morning. Disturbed central dopaminergic signaling has been associated with insulin resistance. Recent studies have demonstrated that in patients with type 2 diabetes (T2D) dopamine D2-receptor agonists improved fasting glucose. However, the precise underlying mechanisms remain unclear.

Here, we investigate if enhancing the morning surge in dopaminergic activity with the dopamine D2 receptor agonist bromocriptine will increase insulin sensitivity, through improving central dopaminergic signaling.

Methods and results

Subjects with T2D ingested bromocriptine once-daily in the morning for 12 weeks. Preliminary analyses of the first 10 subjects showed no significant difference in striatal dopamine D_2/3 Receptor (D_2/3R) availability measured with SPECT imaging (p=0.169) or dopamine release (p=0.262), reflected by the change in D_2/3R availability after dexamphetamine infusion. Additionally, insulin sensitivity, assessed with the two-step hyperinsulinemic-euglycemic clamp, did not show an effect of bromocriptine on basal endogenous glucose production (EGP), insulin-mediated suppression of EGP or peripheral insulin sensitivity (Rd). Fasting glucose showed a downwards trend but was not significant (7.02 (1.68) versus 6.40 (1.13), p=0.132).

Discussion

While this preliminary data does not show an effect of bromocriptine on insulin sensitivity or central dopamine release, there is a downwards trend in fasting glucose which is in line with previous reports. Together, these preliminary findings could suggest the effect of bromocriptine in T2D might be mediated through a different mechanism, such as increased glucose stimulated insulin secretion.