Open Access

Angela Maria Ottomana, Martina Presta, Aet O'Leary, Mairéad Sullivan, Edoardo Pisa, Giovanni Laviola, Jeffrey C. Glennon, Francesca Zoratto, David A. Slattery, Simone Macrì

• Highlights • Hyperglycaemia, in rodents, is consistently associated with cognitive impairments. • The strength of this association is supported by the heterogeneity of the studies. • The study of the role of insulin on cognition is mainly limited to spatial memory. • Preclinical studies on the role of insulin signalling on cognition are male biased. Abstract Beside its involvement in somatic dysfunctions, altered insulin signalling constitutes a risk factor for the development of mental disorders like Alzheimer’s disease and obsessive-compulsive disorder. While insulin-related somatic and mental disorders are often comorbid, the fundamental mechanisms underlying this association are still elusive. Studies conducted in rodent models appear well suited to help decipher these mechanisms. Specifically, these models are apt to prospective studies in which causative mechanisms can be manipulated via multiple tools (e.g., genetically engineered models and environmental interventions), and experimentally dissociated to control for potential confounding factors. Here, we provide a narrative synthesis of preclinical studies investigating the association between hyperglycaemia – as a proxy of insulin-related metabolic dysfunctions – and impairments in working and spatial memory, and attention. Ultimately, this review will advance our knowledge on the role of glucose metabolism in the comorbidity between somatic and mental illnesses.