Evidence map›Paper›PMID 24114586›Full record

ReviewCNS drugs2013

Second generation antipsychotic-induced type 2 diabetes: a role for the muscarinic M3 receptor.

Katrina Weston-Green, Xu-Feng Huang, Chao Deng

Abstract readReview
PubMed Publisher
In one paragraph

Review in CNS drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 4 pooled it
6.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 102 citations in OpenAlex.

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  4. Antipsychotic-induced changes in blood levels of leptin in schizophrenia: a meta-analysis.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2015
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 3 institutions in 1 country.

Katrina Weston-GreenAntipsychotics Research Laboratory, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia, katrina_green@uow.edu.au.
Xu-Feng Huang
Chao Deng
Illawarra Health and Medical Research Institute · AUSchizophrenia Research Institute · AUUniversity of Wollongong · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Second generation antipsychotics (SGAs) are widely prescribed to treat various disorders, most notably schizophrenia and bipolar disorder; however, SGAs can cause abnormal glucose metabolism that can lead to insulin-resistance and type 2 diabetes mellitus side-effects by largely unknown mechanisms. This review explores the potential candidature of the acetylcholine (ACh) muscarinic M3 receptor (M3R) as a prime mechanistic and possible therapeutic target of interest in SGA-induced insulin dysregulation. Studies have identified that SGA binding affinity to the M3R is a predictor of diabetes risk; indeed, olanzapine and clozapine, SGAs with the highest clinical incidence of diabetes side-effects, are potent M3R antagonists. Pancreatic M3Rs regulate the glucose-stimulated cholinergic pathway of insulin secretion; their activation on β-cells stimulates insulin secretion, while M3R blockade decreases insulin secretion. Genetic modification of M3Rs causes robust alterations in insulin levels and glucose tolerance in mice. Olanzapine alters M3R density in discrete nuclei of the hypothalamus and caudal brainstem, regions that regulate glucose homeostasis and insulin secretion through vagal innervation of the pancreas. Furthermore, studies have demonstrated a dynamic sensitivity of hypothalamic and brainstem M3Rs to altered glucometabolic status of the body. Therefore, the M3R is in a prime position to influence glucose homeostasis through direct effects on pancreatic β-cells and by potentially altering signalling in the hypothalamus and brainstem. SGA-induced insulin dysregulation may be partly due to blockade of central and peripheral M3Rs, causing an initial disruption to insulin secretion and glucose homeostasis that can progressively lead to insulin resistance and diabetes during chronic treatment.

Indexed as

AnimalsAntipsychotic AgentsBlood GlucoseDiabetes Mellitus, Type 2HumansInsulinMiceReceptor, Muscarinic M3Antipsychotic AgentsBlood GlucoseInsulinReceptor, Muscarinic M3

Identifiers

PMID24114586
OpenAlexW2005393609

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.