The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated.

Insulin-resistance is one of the main factors responsible for the onset and progression of Metabolic Syndrome (MetS). Among all polyphenols, the effects of flavonoids and their main food sources on insulin sensitivity have been widely evaluated in molecular and clinical studies. The aim of this review is to analyse the data observed in vitro, in vivo and in clinical trials concerning the effects of flavonoids on insulin resistance and to determine the molecular mechanisms with which flavonoids interact with insulin signaling.

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4⁺CD25^high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1⁺, PD-1^low and PD-1^high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1⁺, PD-1^low and PD-1^high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface.

The advanced and performing technologies of glucose monitoring systems provide a large amount of glucose data that needs to be properly read and interpreted by the diabetology team in order to make therapeutic decisions as close as possible to the patient’s metabolic needs. For this purpose, new parameters have been developed, to allow a more integrated reading and interpretation of data by clinical professionals. The new challenge for the diabetes community consists of promoting an integrated and homogeneous reading, as well as interpretation of glucose monitoring data also by the patient himself. The purpose of this review is to offer an overview of the glycemic status assessment, opened by the current data management provided by latest glucose monitoring technologies. Furthermore, the applicability and personalization of the different glycemic monitoring devices used in specific insulin-treated diabetes mellitus patient populations will be evaluated.

Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries. However, this ability diminishes as organisms become more complex. The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions. The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response. Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential. Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments. These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment. The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration. These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration.