Interleukin 6 (IL-6), a multifunctional cytokine, has been implicated in the pathophysiology of type 2 diabetes (T2D). The elevated circulating level of IL-6 is an independent predictor of T2D and is considered to be involved in the development of inflammation, insulin resistance and β-cell dysfunction. On the other hand, an increasing number of evidence suggests that IL-6 has an anti-inflammatory role and improves glucose metabolism. The complex signal transduction mechanism of IL-6 may help explain the pleiotropic nature of the cytokine. IL-6 acts via two distinct signalling pathways called classic signalling and trans-signalling. While both signalling modes lead to activation of the same receptor subunit, their final biological effects are completely different. The aim of this review is to summarize our current knowledge about the role of IL-6 in the development of T2D. We will also discuss the importance of specific blockade of IL-6 trans-signalling rather than inhibiting both signalling pathways as a therapeutic strategy for the treatment of T2D and its associated macrovascular complications.

Breast cancer is the most common cancer among females worldwide and a most prevalent malignancy in Iranian women. Chronic stress may make an important contribution to cancer, especially in the breast. Numerous studies showed roles of neurotransmitters in the occurrence and progression of cancers which are mediated by their various types of receptors. This study was conducted to evaluate alterations in the expression profile of dopamine receptor genes in peripheral blood mononuclear cells (PBMC) as stress factors in breast cancer patients and the human breast cancer cell line (MCF-7). Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total mRNA was extracted from PBMC and MCF-7 cells and RT-PCR was performed to confirm the presence of five dopamine receptors (DRD1-DRD5). Expression changes of dopamine receptor genes were evaluated by real time PCR. We observed that DRD2-DRD4 in PBMCs of breast cancer patients were increased compared to healthy individuals. In addition, all dopamine receptor subtypes but DRD1 were expressed in MCF-7 cells. Therefore, alterations of these receptors as stress factorsshould be assessed for selecting appropriate drugs such as D2-like agonists for treatment of breast cancer after performing complimentary tests. Determining the expression profile of dopamine receptor genes thus seems promising.

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The observed changes in both IL-1β and IL-6 mRNA levels in PBMCs may contribute to the development of inflammatory processes involved in the pathogenesis of T2D. Downregulation of IL1R1 in individuals with mild hyperglycemia may indicate an attempt to reduce the pro-inflammatory effects of IL-1β via auto-stimulation.