title: Dopaminergic drugs in type 2 diabetes and glucose homeostasis.
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.
authors.affiliation: Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Lopez Vicchi
authors.affiliation: Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Guillermina Maria
authors.initials: GM
authors.lastname: Luque
authors.affiliation: Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Belen
authors.initials: B
authors.lastname: Brie
authors.affiliation: Universidad Nacional de Formosa, Facultad de Ciencias de la Salud; Av. Gutnisky 3200-C.P., 3600-Formosa, Argentina.
authors.forename: Juan Patricio
authors.initials: JP
authors.lastname: Nogueira
authors.affiliation: Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia Tornadu
authors.affiliation: Instituto de Biologia y Medicina Experimental CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina. Electronic address: dbecu@dna.uba.ar.
authors.forename: Damasia
authors.initials: D
authors.lastname: Becu-Villalobos
mesh_terms: D000172:Acromegaly / Q000188:drug therapy; D000818:Animals; D001971:Bromocriptine / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy; D011110:Polymorphism, Genetic; D015175:Prolactinoma / Q000188:drug therapy; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D005947:Glucose
keywords: Bromocriptine; Dopamine; Food intake; Glucose; Insulin; Pancreas; Pituitary; Sulpiride