Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes.
Abstract
Second-generation antipsychotics are widely used to medicate patients with schizophrenia, but may cause metabolic side effects such as diabetes, which has been considered to result from obesity-associated insulin resistance. Olanzapine is particularly well known for this effect. However, clinical studies have suggested that olanzapine-induced hyperglycemia in certain patients cannot be explained by such a generalized mechanism. Here, we focused on the effects of olanzapine on insulin biosynthesis and secretion by mouse insulinoma MIN6 cells. Olanzapine reduced maturation of proinsulin, and thereby inhibited secretion of insulin; and specifically shifted the primary localization of proinsulin from insulin granules to the endoplasmic reticulum. This was due to olanzapine's impairment of proper disulfide bond formation in proinsulin, although direct targets of olanzapine remain undetermined. Olanzapine-induced proinsulin misfolding and subsequent decrease also occurred at the mouse level. This mechanism of olanzapine-induced β-cell dysfunction should be considered, together with weight gain, when patients are administered olanzapine.
References
Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review
Cytoplasmic transport signal is involved in phogrin targeting and localization to secretory granules
Luminal interaction of phogrin with carboxypeptidase E for effective targeting to secretory granules
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Antipsychotic Drugs
Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here
Antipsychotic-Induced Weight Gain
Antipsychotic-induced weight gain (aiwg) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. Here are the latest discoveries pertaining to AIWG.