The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes

Growing evidence supports the importance of the p53 tumor suppressor in metabolism but the mechanisms underlying p53-mediated control of metabolism remain poorly understood. Here, we identify the multifunctional E4F1 protein as a key regulator of p53 metabolic functions in adipocytes. While E4F1 expression is upregulated during obesity, E4f1 inactivation in mouse adipose tissue results in a lean phenotype associated with insulin resistance and protection against induced obesity. Adipocytes lacking E4F1 activate a p53-dependent transcriptional program involved in lipid metabolism. The direct interaction between E4F1 and p53 and their co-recruitment to the Steaoryl-CoA Desaturase-1 locus play an important role to regulate monounsaturated fatty acids synthesis in adipocytes. Consistent with the role of this E4F1-p53-Steaoryl-CoA Desaturase-1 axis in adipocytes, p53 inactivation or diet complementation with oleate partly restore adiposity and improve insulin sensitivity in E4F1-deficient mice. Altogether, our findings identify a crosstalk between E4F1 and p53 in the control of lipid metabolism in adipocytes that is relevant to obesity and insulin resistance.

GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans

Epoxyeicosatrienoic acids (EETs) reduce blood pressure by acting in the vasculature and kidney, and interventions to increase circulating EETs improve insulin sensitivity and prevent diabetes in animal models. Inhibition of EET hydrolysis with a sEH (soluble epoxide hydrolase) inhibitor is an attractive approach for hypertension and diabetes. We tested the hypothesis that sEH inhibition increases circulating EETs, reduces blood pressure, and improves insulin sensitivity, blood flow, and inflammation in a randomized, double-blind, placebo-controlled crossover study. Sixteen participants with obesity and prediabetes were randomized to GSK2256294 10 mg QD or placebo for 7 days, insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and adipose and muscle tissues biopsies were performed to assess insulin-stimulated Akt phosphorylation. We assessed tissue and plasma EETs and their respective diol concentrations and sEH activity within plasma, muscle, and adipose tissues. GSK2256294 reduced circulating and adipose tissue sEH activity, but blood pressure, circulating EET, and tissue EETs were unchanged. Plasma sEH activity correlated with muscle and adipose tissue sEH activity. Insulin sensitivity assessed during hyperinsulinemic clamps, as well as adipose and muscle phosphorylated-Akt/Akt expression were similar during GSK2256294 and placebo. sEH inhibition with GSK2256294 reduced plasma F2-isoprostanes (50.7±15.8 versus 37.2±17.3 pg/mL; P =0.03) but not IL (interleukin)-6. Resting blood pressure, forearm blood flow, and renal plasma flow were similar during GSK2256294 and placebo. We demonstrate that GSK2256294 administration for 7 days effectively inhibits sEH activity in plasma, muscle, and adipose tissue and reduces F2-isoprostanes—a marker of oxidative stress—but does not improve insulin sensitivity or blood pressure.

CEGAH AMPUTASI DENGAN PENATALAKSANAAN DIABETES MELITUS DI MASA PANDEMI COVID-19

Background : Diabetes mellitus (DM) is an insulin insufficiency disorder caused by disruption of insulin products by Langerhans beta cells or the body's cells are less responsive to insulin. Covid-19 attacks all ages, especially those who have chronic diseases (co-morbid) have a more frequent risk of getting it with bad complications from this disease. Physical exercise (Diabetes leg exercises) is one of the pillars in the management of DM, which functions to improve insulin sensitivity and maintain body fitness during the COVID-19 pandemic. The goal of this community service is to prevent amputation by managing diabetes mellitus. Method : This community service method refers to action research with the formation of a DM prolanis group at the MERCUBAKTIJAYA clinic in Padang, socialization and education related to the management of diabetes mellitus, as well as monitoring and evaluation that have been carried out in collaboration with the MERCUBAKTIJAYA clinic in Padang as a follow-up to this activity. Result: 90% of the participants were enthusiastic about the activity and were able to re-practice the material presented.

Activation of Insulin Signaling by Botanical Products

Type 2 diabetes (T2D) is a worldwide health problem, ranked as one of the leading causes for severe morbidity and premature mortality in modern society. Management of blood glucose is of major importance in order to limit the severe outcomes of the disease. However, despite the impressive success in the development of new antidiabetic drugs, almost no progress has been achieved with regard to the development of novel insulin-sensitizing agents. As insulin resistance is the most eminent factor in the patho-etiology of T2D, it is not surprising that an alarming number of patients still fail to meet glycemic goals. Owing to its wealth of chemical structures, the plant kingdom is considered as an inventory of compounds exerting various bioactivities, which might be used as a basis for the development of novel medications for various pathologies. Antidiabetic activity is found in over 400 plant species, and is attributable to varying mechanisms of action. Nevertheless, relatively limited evidence exists regarding phytochemicals directly activating insulin signaling, which is the focus of this review. Here, we will list plants and phytochemicals that have been found to improve insulin sensitivity by activation of the insulin signaling cascade, and will describe the active constituents and their mechanism of action.

Prospect for type 2 diabetes mellitus in the combination of exercise and synbiotic: a perspective

: Change in gut microbiome diversity (the so-called dysbiosis) is correlated with insulin resistance conditions. Exercise is typically one of the first management for people with type 2 diabetes mellitus (T2DM), which is generally well-known for improved glucose regulation. The new design of prebiotic and probiotic, like synbiotic form, to target specific diseases is needed for additional studies. While the effectiveness of exercise and the combination of exercise and synbiotic prescription seems promising, this review discusses the possibility of these agents to increase the diversity of gut microbiota and therefore could enhance short-chain fatty acid (SCFA). In particular, the interaction of synbiotic towards gut microbiota, the mechanism of exercise in improving gut microbiota, and the prospect of the synergistic effect of the combination of synbiotic and exercise to improve insulin sensitivity is addressed.