Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes

Abstract

Neuropsychiatric disorders and type 2 diabetes (T2D) are major public health concerns proposed to be intimately connected. T2D is associated with increased risk of dementia, neuropsychiatric and mood disorders. Evidences of the involvement of insulin signaling on brain mechanisms related to depression indicate that insulin resistance, a hallmark of type 2 diabetes, could develop in the brains of depressive patients. In this article, we briefly review possible molecular mechanisms associating defective brain insulin signaling with reward system, neurogenesis, synaptic plasticity and hypothalamic-pituitary-adrenal (HPA) stress axis in depression. We further discuss the involvement of tumor necrosis factor α (TNFα) promoting defective insulin signaling and depressive-like behavior in rodent models. Finally, due to the high resistant rate of anti-depressants, novel insights into the link between insulin resistance and depression may advance the development of alternative treatments for this disease.

The Effect of a Maternal Mediterranean Diet in Pregnancy on Insulin Resistance is Moderated by Maternal Negative Affect

“…Elevated proinflammatory cytokines are involved in the pathogenesis of insulin resistance. For example, TNF-alpha induces phosphorylation of the insulin receptor substrate 1 on serine residues via activation of cellular stress response kinases, leading to insulin signaling impairment [56][57][58]. A low-grade inflammatory state has also been shown to induce adipose tissue insulin resistance in late pregnancy [59].…”

Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression—A Literature Review

“…A body of evidence has addressed the correlation between depression and T2D. Although evidence from epidemiological studies strongly suggests reciprocal associations between the two conditions [13,72,73], various confounding factors implicated in their comorbidity complicate the association [7]. However, several possible molecular links between depression and diabetes have been identified.…”

“…Therefore, there remains a need to elucidate novel targets that may yield improved efficacy, tolerability and, possibly, disease modifying effects. The insulin signaling system has been proposed as a novel target in the treatment of depression [7][8][9]. Because a bi-directional association between diabetes/insulin resistance and depression has been described in many studies [9][10][11][12][13], an underlying shared pathophysiologic mechanism of depression and type 2 diabetes mellitus (T2DM) and anti-depressant effects of anti-diabetic agents have been explored in the field.…”

Fermented Butyrate of Aloe vera and A. arborescens by Endophytic Bacteria: Its Prophylactic Action on Brain Insulin Resistance

“…Evidences of the involvement of insulin signaling on brain mechanisms related to depression indicate that insulin resistance, a hallmark of T2D, could develop in the brains of depressive patients. Lyra E Silva et al [31] discussed possible molecular mechanisms associating detective brain insulin signaling with reward system, neurogenesis, synaptic plasticity and hypothalamic-pituitary-adrenal stress axis in depression. Due to the high resistance rate of anti-depressants, novel insights into the link between insulin resistance and depression may advance the development of alternative treatments for this disease.…”