Diabetes and diabesity in the view of proteomics, drug, and plant-derived remedies.

Diabetes and obesity are highly prevalent in the world. Proteomics is a promising approach to better understanding enzymes, proteins, and signaling molecules involved in diabetes processes which help recognize the basis of the disease better and find suitable new treatments. This study aimed to summarize the molecular mechanisms from the beginning of insulin secretion in response to stimuli to the pathology of the insulin signaling pathway and, finally, the mechanisms of drugs/chemicals remedies that affect this process. The titles and subtitles of this process were determined, and then for each of them, the articles searched in PubMed and ScienceDirect were used. This review article starts the discussion with the molecular basis of insulin biosynthesis, secretion, insulin's mechanism of action, and molecular aspect of diabetes and diabesity (a new term showing the relation between diabetes and obesity) and ends with the drug and plant-derived intervention for hyperglycemia.

Implementation of a method for a clinical biochemistry lesson plan based on the flowchart.

Biochemistry is believed to be a difficult subject to understand for most life science and medical students. This article explains an experience with a flowchart-based teaching approach that is applicable to different kinds of biochemistry courses (basic, medical, and clinical) for undergraduate and postgraduate students. After preparing the flowcharts, they were given to the students at the beginning of the semester, and the flowchart-based teaching was performed for a whole semester. At the end of the semester, they were asked about the effectiveness and facilitation of learning using flowchart-based teaching. This survey was performed for several semesters. Approximately, 95% stated that it facilitates learning and understanding.

Antibacterial Effect of Some Eukaryotic Sterol Biosynthesis Inhibitors.

Background: Isoprenoids and their derivatives are building blocks for the synthesis of biomolecules with important biological functions such as cholesterol in eukaryotes and lipid carrier undecaprenol, which is involved in cell wall biosynthesis in bacteria. With the global threat of multidrug-resistant bacteria, there is a need for finding new metabolic targets for killing bacteria. In the present study, we examined the impact of eukaryotic sterol biosynthesis inhibitors on the growth of four pathogenic bacteria. Materials and Methods: Antibacterial effect of HMG CoA reductase inhibitor (simvastatin), farnesyl pyrophosphate synthase inhibitor (alendronate), squalene epoxidase inhibitor (terbinafine), and lanosterol demethylase inhibitor (ketoconazole) were studied against four pathogenic bacteria: two gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis and two gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa. Broth microdilution method was used for assessing the antibacterial susceptibility of the components using 96 well plats. MIC and MBC were determined visibly. Results: MIC of Ketoconazole for Staphylococcus aureus and Enterococcus faecalis were 0.166 and 1 mg/mL, respectively. Terbinafine had a weak inhibitory effect on Staphylococcus aureus (MIC: 8 mg/mL). Ketoconazole and terbinafine had no inhibitory effect on gram-negative bacteria. MBC of Simvastatin for both Staphylococcus aureus and Enterococcus faecalis was 0.5 mg/mL and of Alendronate for Pseudomonas aeruginosa was 6.6 mg/mL. Conclusion: Our results show that farnesyl pyrophosphate synthase and class II HMG-CoA reductases inhibitors (ketoconazole and simvastatin) have reasonable antibacterial activity against gram-positive bacteria. These two enzymes provide suitable targets for designing new antibiotics based on modifying the chemical structure of currently used drugs to obtain maximum activity.

The Effect of Long-Term Iron Chelator Therapy on Serum Levels of Hepcidin and Ferritin in Patients with Thalassemia Major and Intermediate.

Serum hepcidin is a good predictor of iron overload compared with serum ferritin. However, serum hepcidin levels may change under different conditions. The current study aims to determine the role of long-term iron chelator therapy on serum levels of hepcidin and ferritin in patients with thalassemia major (TM) and intermediate (TI). In this cross-sectional study 91 patients with thalassemia TM and TI, who referred to the thalassemia center were chosen. The serum levels of hepcidin and ferritin were measured after two years of iron chelator therapy by ELISA and ECL methods, respectively. The patients' demographic information was extracted from their records. After treatment with iron chelator, ferritin levels decreased in 44 patients (48.4%), and increased in 47 patients (%51.6). Median serum levels of hepcidin decreased in all patients (%100). Also, there was a significant association between serum levels of hepcidin and ferritin (p value = 0.034). Furthermore, while a significant difference was observed between ferritin changes (p = 0.01), no difference was found between changes in hepcidin based on the type of iron chelator (p value = 0.94). Increased levels of hepcidin and ferritin in ß-thalassemia patients are significantly ameliorated by iron chelator.

Magnesium supplementation and insulin resistance in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a multifactorial disease affecting the immune system and many tissues in the body. This study aimed to evaluate the effect of magnesium supplementation on insulin resistance and fasting blood sugar (FBS) of patients with RA. In this prospective uncontrolled before-after study, RA patients referring to Rheumatology clinics of Qom City from January 2020 to January 2021 were evaluated. First, the patients received the routine rheumatoid arthritis treatment including 5 mg Prednisolone and 200mg Hydroxychloroquine daily for 6 months and FBS and insulin levels were measured after. Then, they received the routine arthritis rheumatoid treatment in addition to 300 mg/day oral Magnesium sulfate for 6 months and then, FBS and insulin levels were measured. The Homeostasis Model Assessment of insulin resistance (HOMA-IR) was used for determining insulin resistance. Thirty five patients with RA and the mean age of 49.83±2.58 years were enrolled. Twenty eight cases (80%) were female and 7 cases (20%) were male. The mean HOMA-IR before and after consumption of oral magnesium were 3.04±0.29 and 2.43±0.19, respectively. Statistically significant differences were found between FBS, insulin and HOMA-IR before and after consumption of oral magnesium (p<0.05). Our data suggested that magnesium supplementation reduces FBS, insulin and HOMA-IR in patients with rheumatoid arthritis. Thus, magnesium supplements may be an alternative method for prevention of type 2 diabetes in RA patients.

Anti-diabetic effect of Capparis spinosa L. root extract in diabetic rats.

OBJECTIVE: Diabetes mellitus is the most common metabolic disorders with severe impact on quality of life. Reducing serum glucose levels and normalization of serum lipid is of great clinical importance for treating diabetes. To our knowledge, there are not any evidences about the anti-diabetic action of capparis spinosa root. In the present study the effects of the C. spinosa root extract on diabetic metabolic disorders have been studied in experimental diabetes. MATERIALS AND METHODS: Rats were divided into six groups: normal control (NC), diabetic control (DC), diabetic rats receiving 0.2, 0.4 g/kg of plant extract or 0.6 mg/kg glibenclamide (groups D0.2, D0.4 or DG respectively). A normal group of rats was also designed to receive 0.2 g/kg of plant extract (N0.2). Rats were rendered diabetic (streptozotocin 60 mg/kg, i.p.) and treated with 0.2, 0.4 g/ kg of plant extract or glibenclamide for four weeks. At the end of the experiment, blood was drawn through heart puncture under deep anesthesia. Weight was measured weekly, glucose levels were measured at the first and fourth week and lipid profiles, insulin and liver enzymes at the end of the study. RESULTS: Glucose levels significantly decreased after treating with plant extract (p=0.003). However, insulin levels did not increase in any treating groups. Plant extract could significantly raise HDL and reduce levels of LDL and liver enzymes (ALT and ALP). CONCLUSION: These results showed that C. spinosa root extract could improve diabetic related metabolic derangement such as hyperglycemia, dyslipidemia, and elevated liver markers in an insulin-independent manner.

Nonselective mevalonate kinase inhibitor as a novel class of antibacterial agents.

Introduction. There are a few evidences about targeting isoprenoids biosynthesis pathway in bacteria for finding new antibiotics. This study was conducted to assess antibacterial effects of vanadyl sulfate (VS), one of the mevalonate kinase inhibitors to find a new target for killing bacteria. Materials and Methods. Antibacterial effect of VS alone and in combination with glycine or EDTA was assessed on Escherichia coli and Pseudomonas aeruginosa as Gram-negative and Staphylococcus aureus and Enterococcus faecalis as Gram-positive bacteria using serial dilution method and minimum inhibitory concentrations (MICs) identified. Result. MICs for S. aureus and E. coli were 4 and 8 mg/mL, respectively. VS could not affect the growth of two other bacteria. However, VS in combination with glycine not only inhibited the growth of E. faecalis and P. aeruginosa, but also reduced MICs for VS-sensitive bacteria (S. aureus and E. coli). EDTA could reduce MIC for E. coli and P. aeruginosa. Conclusion. VS could inhibit the growth of S. aurous and E. coli, and adding glycine or EDTA improved VS antibacterial activity presumably via instability of the cell wall and enhanced transport of VS through bacterial cell wall. Inhibition of the isoprenoid pathway might provide new tools to overcome bacterial resistance.

Cholesterol suppresses antimicrobial effect of statins.

OBJECTIVES: Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. MATERIALS AND METHODS: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria using gel diffusion assay. RESULTS: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. CONCLUSION: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

The effect of fenugreek 4-hydroxyisoleucine on liver function biomarkers and glucose in diabetic and fructose-fed rats.

Fenugreek (Trigonella foenum graecum L) is a plant traditionally used for the treatment of diabetes. It contains an unusual amino acid, 4-hydroxyisoleucine, demonstrated to have insulinotropic and antidiabetic properties in animal models. Here we examine the effect of 4-hydroxyisoleucine on liver function and blood glucose in two rat models of insulin resistance, fructose-fed rats and streptozotocin-induced diabetes type 2. In fructose-fed rats, levels of glucose and liver damage marker aspartate transaminase were markedly (84% and 93%, respectively) and significantly elevated compared with controls (p < 0.001 for both). Alanine transaminase was elevated slightly (18%), and all markers were restored to near control values after treatment with 4-hydroxyisoleucine at 50 mg/kg per day for 8 weeks, the effect being significant (p < 0.01) for all markers. This prolonged exposure to 4-hydroxyisoleucine was well tolerated in control animals and did not alter levels of glucose or liver damage markers significantly. In diabetic rats, treatment with 4-hydroxyisoleucine did not affect glucose or liver damage markers, but did improve HDL-cholesterol levels (31% increase, p < 0.05). These findings indicate 4-hydroxyisoleucine as a useful and well-tolerated treatment for insulin resistance, both directly as a hypoglycaemic and also as a protective agent for the liver.