Integrating insulin-like growth factor 1 and sex hormones into neuroprotection: Implications for diabetes

Abstract

Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1 (IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sex-hormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinase signaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones.

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…Leptin is closely linked with several growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor 21 (FGF21), and insulin-like growth factor-1 (IGF-1) [5], [6], [7] (Table 1) [1], [4], [8], [9], [10], [11]. A study on human subjects detected an increased gene expression of leptin and IGF-1 in the subcutaneous fat of the obese group, while the expression of IGF-1 in the visceral fat was higher in the control group (non-obese cholecystectomy cases) [12].…”

Is sex an influential factor in type‐1 diabetes neurofunctional development? A preliminary study

“…More recently, it has been suggested that sex hormones may play a strong modulatory role in explaining sex differences in cerebral perfusion (Ghisleni et al, ). Still, it has been proposed that female sex hormones could have a neuroprotective effect, given that fluctuations in these hormones are observed in patients with diabetes and may contribute to abnormalities in brain integrity and cognitive impairment (Huffman, Hoffmann, & Taylor, ). The interaction of these factors is most likely very complex.…”

“…The development of T1DM might affect working memory and consequently the performance of VSWM tasks. On the one hand, by prompting higher and more extensive brain functional activation, while on the other hand, the increased cerebral blood flow (Esposito et al, ) and the neuroprotective effect of female hormones (Huffman et al, ) might facilitate distinctive activations probably related to the development of an adaptive cognitive strategy. This phenomenon could imply a sex advantage, yet should be further explored since recent studies have also reported that in spite of this relative hormonal protection, adult women with T1DM have a greater risk of stroke (37%) and are 44% more likely to die from kidney disease than men with the disorder (Huxley et al, ).…”

New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection

“…ER-α and IGF-IR co-activation may mediate neuroprotection, and many other growth factors and intracellular signaling responses triggered by ER-α may play important roles in the process [98].These data are crucial for contemporary societies, with high risks for diabetes mellitus, in all populations. A very recent study from the University of Missouri, St. Louis (USA) [99] demonstrated the neuroprotection of the coupling of IGF1 to estrogens and/androgens. It is considered that both steroids are involved in many neuroprotective processes that operate on similar signaling cascades [100].…”