Table 2.

Summary of the literature review results (animal models and cell lines)

Author	Year	Country	Aim	Methodology	Sample size	Subjects	Antipsychotics	Duration	Key findings
Shamshoum et al. [30]	2021	Canada	To review the peripheral mechanisms of acute olanzapine-induced related metabolic disturbances	Narrative review			Clozapine and olanzapine		Preclinical in vivo studies in this review revealed gender-specific changes in glucose metabolism in response to Aps
Ren et al. [28]	2019	China	To investigate olanzapine-induced insulin-desensitivity in the liver	Animal study		Rats	Olanzapine		IRS/PI3K/Akt signaling pathway mediates olanzapine-induced hepatic insulin resistance in male rats
Nagata et al. [41]	2018	Japan	To clarify the mechanism of clozapine-induced acute hyperglycemia	Animal study		Wistar rat	Clozapine		Single clozapine administration raised rat serum glucose levels
Liu et al. [31]	2017	Australia	To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use for 9 weeks in rats	Animal study		Rat	Clozapine and olanzapine		SGA-induced glucose-lipid metabolic disturbances may occur independently of weight gain, potentially via liver SREBP/ChREBP activation
Castellani et al. [43]	2017	Canada	To investigate glucagon’s role in mediating olanzapine-induced blood glucose increase	Animal study		WT mice, Gcgr-/- mice	Olanzapine		Central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis
Mondelli et al. [29]	2013	UK	To find the molecular pathways of haloperidol- and olanzapine-induced metabolic abnormalities	Animal study		Sprague-Dawley rat	Olanzapine and haloperidol		Different molecular pathways mediate glucose homeostasis disturbances induced by haloperidol and olanzapine, with olanzapine directly affecting the insulin pathway
Panariello et al. [33]	2012	Italy	To investigate the effect of clozapine on insulin action by analyzing insulin signaling in vitro and in vivo	Laboratory and animal study		PCI2, L6 cells and C57/BL/KsJ mice	Clozapine		Clozapine impairs insulin signaling and glucose uptake by affecting Akt and PKC-z
Smith et al. [42]	2009	New Zealand	To compare the effects of clozapine and quetiapine on the development of obesity and glucose metabolism.	Animal study		Sprague-Dawley rat	Clozapine and quetiapine		Clozapine and quetiapine impair glucose tolerance in rats independently of obesity-induced insulin resistance
Smith et al. [40]	2008	New Zealand	To investigate the impact of SGAs on glucose metabolism	Animal study		Rat	Haloperidol, quetiapine, and clozapine		SGAs induce acute disruptions in glucose metabolism through increased glucagon secretion
Engl et al. [32]	2005	Austria	To find pathogenesis of SGA-induced disturbance of glucose homeostasis	Laboratory study		L6 skeletal muscle cell	Olanzapine		Olanzapine reduces glycogen content in L6 cells by inhibiting insulin signaling

DM, diabetes mellitus; DKA, diabetic ketoacidosis; FGAs, first-generation antipsychotics; SGAs, second-generation antipsychotics; APs, antipsychotics; WP, wild type