How can antipsychotics cause Diabetes Mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins.
The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.
Starrenburg
F C J
FC
Rivierduinen Psychiatric Centre, Midden Holland District, JP Thijsselaan 45, 2803RT Gouda, Netherlands. f.starrenburg@ggzmiddenholland.nl
Bogers
J P A M
JP
D052242:Adiponectin / Q000378:metabolism; D014150:Antipsychotic Agents / Q000009:adverse effects*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000009:adverse effects; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects; D015363:Quinolones / Q000009:adverse effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D013844:Thiazoles / Q000009:adverse effects; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D014150:Antipsychotic Agents; D001786:Blood Glucose; D020738:Leptin; D010879:Piperazines; D015363:Quinolones; D043587:Receptor, Muscarinic M3; D017448:Receptors, Dopamine D2; D011968:Receptors, Histamine; D058825:Serotonin 5-HT1 Receptor Agonists; D013844:Thiazoles; D044282:Receptor, Serotonin, 5-HT1A; D001569:Benzodiazepines; C092292:ziprasidone; D000068180:Aripiprazole; D003024:Clozapine; D000077152:Olanzapine