Dopaminergic drugs in type 2 diabetes and glucose homeostasis

Pharmacol Res. 2016 Jul;109:74-80. doi: 10.1016/j.phrs.2015.12.029. Epub 2015 Dec 31.

Abstract

The importance of dopamine in central nervous system function is well known, but its effects on glucose homeostasis and pancreatic β cell function are beginning to be unraveled. Mutant mice lacking dopamine type 2 receptors (D2R) are glucose intolerant and have abnormal insulin secretion. In humans, administration of neuroleptic drugs, which block dopamine receptors, may cause hyperinsulinemia, increased weight gain and glucose intolerance. Conversely, treatment with the dopamine precursor l-DOPA in patients with Parkinson's disease reduces insulin secretion upon oral glucose tolerance test, and bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients as well as in non diabetic obese animals and humans. The actions of dopamine on glucose homeostasis and food intake impact both the autonomic nervous system and the endocrine system. Different central actions of the dopamine system may mediate its metabolic effects such as: (i) regulation of hypothalamic noradrenaline output, (ii) participation in appetite control, and (iii) maintenance of the biological clock in the suprachiasmatic nucleus. On the other hand, dopamine inhibits prolactin, which has metabolic functions; and, at the pancreatic beta cell dopamine D2 receptors inhibit insulin secretion. We review the evidence obtained in animal models and clinical studies that posited dopamine receptors as key elements in glucose homeostasis and ultimately led to the FDA approval of bromocriptine in adults with type 2 diabetes to improve glycemic control. Furthermore, we discuss the metabolic consequences of treatment with neuroleptics which target the D2R, that should be monitored in psychiatric patients to prevent the development in diabetes, weight gain, and hypertriglyceridemia.

Keywords: Bromocriptine; Dopamine; Food intake; Glucose; Insulin; Pancreas; Pituitary; Sulpiride.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy
  • Animals
  • Bromocriptine / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Dopamine Agents / adverse effects
  • Dopamine Agents / therapeutic use*
  • Glucose / metabolism*
  • Homeostasis
  • Humans
  • Parkinson Disease / drug therapy
  • Polymorphism, Genetic
  • Prolactinoma / drug therapy
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism

Substances

  • Dopamine Agents
  • Receptors, Dopamine D2
  • Bromocriptine
  • Glucose