Development of diabetes generally reflects an inadequate mass of insulin‐producing β‐cells. β‐cell proliferation and differentiation are regulated by a variety of growth factors and hormones, including insulin‐like growth factor I (IGF‐I). GRF1 is a Ras‐guanine nucleotide exchange factor known previously for its restricted expression in brain and its role in learning and memory. Here we demonstrate that GRF1 is also expressed in pancreatic islets. Interest ingly, our GRF1‐deficient mice exhibit reduced body weight, hypoinsulinemia and glucose intolerance owing to a reduction of β‐cells. Whereas insulin resistance is not detected in peripheral tissues, GRF1 knockout mice are leaner due to increased lipid catabolism. The reduction in circulating insulin does not reflect defective glucose sensing or insulin production but results from impaired β‐cell proliferation and reduced neogenesis. IGF‐I treatment of isolated islets from GRF1 knockouts fails to activate critical downstream signals such as Akt and Erk. The observed phenotype is similar to manifestations of preclinical type 2 diabetes. Thus, our observations demonstrate a novel and specific role for Ras‐GRF1 pathways in the development and maintenance of normal β‐cell number and function.

Nowadays, obesity is considered as one of the main concerns for public health worldwide, since it encompasses up to 39% of overweight and 13% obese (WHO) adults. It develops because of the imbalance in the energy intake/expenditure ratio, which leads to excess nutrients and results in dysfunction of adipose tissue. The hypertrophy of adipocytes and the nutrients excess trigger the induction of inflammatory signaling through various pathways, among others, an increase in the expression of pro-inflammatory adipocytokines, and stress of the endoplasmic reticulum (ER). A better understanding of obesity and preventing its complications are beneficial for obese patients on two facets: treating obesity, and treating and preventing the pathologies associated with it. Hitherto, therapeutic itineraries in most cases are based on lifestyle modifications, bariatric surgery, and pharmacotherapy despite none of them have achieved optimal results. Therefore, diet can play an important role in the prevention of adiposity, as well as the associated disorders. Recent results have shown that flavonoids intake have an essential role in protecting against oxidative damage phenomena, and presents biochemical and pharmacological functions beneficial to human health. This review summarizes the current knowledge of the anti-inflammatory actions and autophagic flux of natural flavonoids, and their molecular mechanisms for preventing and/or treating obesity.

AIM--To determine whether iron metabolism influences the incidence of systemic fungal infection in patients with haematological malignancies. METHODS--The study population comprised 74 patients who had undergone myeloablative chemotherapy. Systemic fungal infections were classified as confirmed (histological confirmation or characteristic septate hyphae) or possible (antibiotic resistant fever which resolved following administration of intravenous amphotericin B, together with either typical radiographic lesions or massive oropharyngeal candidiasis). Parameters of iron metabolism included serum iron concentrations, total iron binding capacity, serum transferrin, and ferritin concentrations and transferrin saturation values. RESULTS--Patients who developed a fungal infection had substantially increased transferrin saturation values and ferritin concentrations at diagnosis together with low serum transferrin and high serum iron concentrations. This profile was present in patients with a fungal infection regardless of the underlying haematological disorder. CONCLUSION--Increased transferrin saturation values and high ferritin concentrations may be additional risk factors for the development of systemic fungal infection in patients with haematological malignancies.

The local synthesis of dopamine and its effects on insulin release have been described in isolated islets. Thus, it may be accepted that dopamine exerts an auto-paracrine regulation of insulin secretion from pancreatic beta cells. The aim of the present study is to analyze whether dopamine is a regulator of the proliferation and apoptosis of rat pancreatic beta cells after glucose-stimulated insulin secretion. Glucose stimulated pancreatic islets obtained from male Wistar rats were cultured with 1 or 10 μM dopamine from 1 to 12 h. Insulin secretion was analyzed by RIA. The cellular proliferation rate of pancreatic islets and beta cells was studied with immunocytochemical double labelling for both insulin and PCNA (proliferating cell nuclear antigen), and active caspase-3 was detected to evaluate apoptosis. The secretion of insulin from isolated islets was significantly inhibited (p<0.01), by treatment with 1 and 10 μM dopamine, with no differences between either dose as early as 1 h after treatment. The percentage of insulin-positive cells in the islets decreased significantly (p<0.01) after 1 h of treatment up to 12 h. The proliferation rate of insulin-positive cells in the islets decreased significantly (p<0.01) following treatment with dopamine. Apoptosis in pancreatic islets and beta cells was increased by treatment with 1 and 10 μM dopamine along 12 h. In conclusion, these results suggest that dopamine could modulate the proliferation and apoptosis of pancreatic beta cells and that dopamine may be involved in the maintenance of pancreatic islets.