Potential role of insulin on the pathogenesis of depression

Abstract

| INTRODUC TI ONDiabetes is a metabolic disease characterized by hyperglycaemia due to the defect of insulin secretion or impaired insulin biological effect. A survey has shown that about 30% of people with diabetes also suffer from depression and 10% have severe depression, which suggests a close relationship between the two diseases. 1,2 The mechanism of depression as a complication of diabetes is not completely clear, but studies have found that insulin deficiency or insulin resistance is the symptom that can also be observed in major depression disorder. [3][4][5] Insulin is the only hormone in the human body that reduces the blood glucose level and promotes the synthesis of glycogen, fat and protein. Several studies found that insulin had the ability to affect the nervous system. 6-8 Insulin receptors were distributed in other parts of the brain, except for the parts related to food intake and energy. 9-11 Experiments have gradually revealed other functions of insulin in the brain, for instance promoting memory, protecting neurons, regulating synaptic plasticity and maintaining HPA axis homeostasis. [12][13][14] These effects of insulin may provide a background for its relationship with depression. 15,16 In this case, although there is no direct evidence supporting the link between insulin and treatment for depression, more and more researches support this hypothesis. Here, we review the relationship between insulin signalling and neurophysiological homeostasis, neurotrophic metabolism, cellular pathways and some survey statistics.The exploration of these links and the validation of more relevant mechanisms will develop a new impact on the way of the diagnosis and treatment of depression. | IN SULIN AND DEPRE SS I ONAs early as 1980s, many evidences proved that insulin influenced depression and functional insulin receptors were widely present in the brain. [17][18][19] Data from clinical and epidemiological studies demonstrate a two-way link between emotion and metabolic dysfunction. In young depression patients, insulin sensitivity is significantly decreased. 20,21 Compared with "low insulin" (1.5 mU/kg × min), "high insulin" (15 mU/kg × min) induces a more pronounced of the ability to remember word lists in human being. 22 Intranasal delivery of insulin in awake mice can transmit regulatory and metabolic AbstractThe regulation of insulin on depression and depression-like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic-pituitary-adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.

Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

“…Increased HbA1c levels without associated obesity or signs of insulin resistance in the depressed patients could be due to inadequate insulin supply. Insulin deficiency has been suggested as one reason for the development of depression in patients with T1DM [ 7 , 45 ]. Users of MDII compared to users of CSII had more often low levels of sTWEAK.…”

Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

“…Increased HbA1c levels without associated obesity or signs of insulin resistance in the depressed patients could be due to inadequate insulin supply. Insulin de ciency has been suggested as one reason for the development of depression in patients with T1DM [7,45]. Users of MDII compared to users of CSII had more often low levels of sTWEAK.…”

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

“…One of the mechanisms by which insulin affects the HPA axis is in its effect on blood glucose [173]. When insulin does not effectively lower blood glucose, its effect on the HPA axis is diminished [166]. These results suggest that the bidirectional physiological link between depression and diabetes is likely to involve the HPA axis.…”

“…In general, GCs mobilize energy substrates such as lipids and glucose, increasing their levels in systemic circulation [164]. Physiologically, GCs promote insulin secretion [165]; conversely, insulin activates the HPA axis and leads to an increase in GC levels and corticotropin releasing hormone (CRH) levels [166]. Increases in CRH by insulin are mediated through activation of the cyclic adenosine monophosphate (cAMP)/AMP protein kinase A (PKA) and PI3K/AKT pathways; this activation, in turn, affects CRH promoters, stimulates CRH gene transcription, and increases CRH levels [166].…”

“…Recent evidences indicate that gut microbes and insulin interact with each other. Reducing insulin resistance could maintain the homeostasis of gut microbiota and restore intestinal microbiome disorders [166]. Inversely, modulation of gut microbiota could improve glucose metabolism and insulin resistance by adjusting the microbiota-gut-brain axis [174].…”