Insulin-like Action Research Articles

Comparative Efficacy Study of N-Chromosome Royal Jelly Versus Semelil (ANGIPARS) on Wound Healing of Diabetic Rats

Objective: The healing effects of two different dilutions (5 & 100%) of N-Chromosome Royal Jelly and ANGIPARS ointment were investigated and measured on experimental injuries in streptozotocin (STZ)- induced diabetic rats. This study investigated the healing effects of 2 different N Chromosome Royal Jelly dilutions on injuries of STZ-induced diabetic rats.
 Materials and Methods: For diabetes induction, male Wistar rats received STZ (55 mg/kg) intraperitoneally and plasma glucose level measurement after 72 hours demonstrated diabetes induction. Rats were randomly divided into 5 groups of 6 members and one square centimeter (cm2 ) wound was surgically induced in the dorsal region of each rat. The test groups were treated with ANGIPARS, undiluted royal jelly N chromosome, and royal jelly N chromosome 5% separately. The control groups were including non-diabetic and untreated diabetic rats.
 Results: The findings indicate a significant acceleration in wound healing of the diabetic rats treated by ANGIPARS ointment or royal jelly N chromosomes 5%. RJ also shortened the healing period of desquamated skin lesions. Thus, RJ possesses an anti-inflammatory action and is able to augment wound healing, but does not have an insulin-like action in streptozotocin-diabetic rats.
 Conclusion: Regarding the mentioned findings, royal jelly as a natural product may play an effective role in treating chronic wounds in mice, which makes it a proper candidate for use in human wound repair. Nonetheless, it seems that determination of the suitable dilution of this compound will result in better effects, thus more studies are recommended.

Effects of Chemical Structures Interacting with Amine Oxidases on Glucose, Lipid and Hydrogen Peroxide Handling by Human Adipocytes.

Benzylamine is a natural molecule present in food and edible plants, capable of activating hexose uptake and inhibiting lipolysis in human fat cells. These effects are dependent on its oxidation by amine oxidases present in adipocytes, and on the subsequent hydrogen peroxide production, known to exhibit insulin-like actions. Virtually, other substrates interacting with such hydrogen peroxide-releasing enzymes potentially can modulate lipid accumulation in adipose tissue. Inhibition of such enzymes has also been reported to influence lipid deposition. We have therefore studied in human adipocytes the lipolytic and lipogenic activities of pharmacological entities designed to interact with amine oxidases highly expressed in this cell type: the semicarbazide-sensitive amine oxidase (SSAO also known as PrAO or VAP-1) and the monoamine oxidases (MAO). The results showed that SZV-2016 and SZV-2017 behaved as better substrates than benzylamine, releasing hydrogen peroxide once oxidized, and reproduced or even exceeded its insulin-like metabolic effects in fat cells. Additionally, several novel SSAO inhibitors, such as SZV-2007 and SZV-1398, have been evidenced and shown to inhibit benzylamine metabolic actions. Taken as a whole, our findings reinforce the list of molecules that influence the regulation of triacylglycerol assembly/breakdown, at least in vitro in human adipocytes. The novel compounds deserve deeper investigation of their mechanisms of interaction with SSAO or MAO, and constitute potential candidates for therapeutic use in obesity and diabetes.

Effects of Raw and Pasteurized Camel Milk on Metabolic Responses in Pigs Fed a High-Fat Diet.

Simple SummaryCamel milk (CM) contains insulin-like peptides and is high in vitamin C, vitamin E, and antioxidants. Previous studies in diabetic mice and humans have demonstrated a positive impact of CM consumption on glycemic balance, potentially greater than that observed for the consumption of bovine milk. Thus, CM may be a viable therapeutic treatment for diabetic humans, although the mode of action of these effects are not yet understood. This experiment used a high-fat diet as a monogastric model to examine the effect of CM consumption (raw or pasteurized) on some key blood metabolic markers and examined responses to an in vitro glucose tolerance test. While the results are preliminary given the low number of animals, this experiment suggested that CM can improve glycemic control, potentially via a tighter control of insulin effectiveness and/or uptake.Evidence suggests that camel milk (CM) can have insulin-like actions, although the mode of action is not understood. Using the pig as a monogastric model, this pilot experiment examined the effects of CM consumption on metabolic responses to an in vitro glucose tolerance test (IVGTT). Twenty female Large White × Landrace pigs were individually housed for 6 wks and randomly allocated to one of the following four diets (fed ad libitum; n = 5): control (Con); high fat (HF; ~16% fat); raw CM (the HF diet plus 500 mL CM/ day); or pasteurized CM (PCM). Blood samples were collected on two occasions (weeks 2 and 5). At week 6, the pigs were fitted with an ear vein cannula and the following day an in vitro glucose tolerance test (IVGTT) was conducted (0.3 g/kg BW glucose). Plasma fatty acids and cholesterol concentrations were greater in the pigs fed the HF diet and greatest in those fed CM, while there was no effect of diet on insulin concentrations. The pigs fed CM tended to have a reduced peak insulin (p = 0.058) and an increased glucose nadir (p = 0.009) in response to the IVGTT. These preliminary results tend to support the hypothesis that feeding CM can improve glycemic control in pigs.

THE ROLE OF CATESTATIN IN THE REGULATION OF METABOLIC DISORDERS. Review

Relevance. Cardiovascular diseases occupy leading positions in the structure of morbidity and mortality both in Ukraine and in other countries. Metabolic disorders are one of the leading risk factors for the development and progression of cardiovascular diseases. In accordance with the above-mentioned special attention should be paid to catestatin, which regulates carbohydrate and lipid metabolism, that determines its diagnostic potential in the management of diseases, which are accompanied by metabolic dysregulation.
 Objective: Determination of the diagnostic potential of catestatin in the management of diseases associated with metabolic disorders such as type 2 diabetes mellitus, obesity and metabolic syndrome, in accordance with its role in the regulation of metabolic homeostasis based on the analysis of data literature sources.
 Methods. Analysis of the research results by reviewing electronic scientometric databases PubMed and Google Scholar by keywords.
 Results. The influence of catestatin on the pathogenetic mechanisms of cardiometabolic diseases is analyzed. The general characteristic of catestatin and its physiological properties is given. The effect of catestatin on carbohydrate metabolism due to its insulin-like action is studied, which in combination with antioxidant, immunomodulatory and anti-inflammatory action of catestatin determines its role in the regulation of glucose metabolism. The property of catestatin to regulate cardiometabolic homeostasis by modulating the bioenergetic activity of the myocardium is noted. Mechanisms of regulation of fat metabolism by catestatin are established, in particular, realization of its lipolytic effect due to suppression of α2-adrenoreceptors and regulation of adrenergic and leptin signaling. Correlations between catestatin levels and lipid profile and anthropometric data are considered. Typical changes in catestatin levels at the development of cardiometabolic diseases are defined.
 Conclusions. Catestatin has metabolic effects, in particular, participates in the regulation of carbohydrate and lipid metabolism, which determines its prognostic role in the development and progression of cardiometabolic diseases.

L-Arginine’s Glucose Homeostatic Influence in Renal Damaged Wistar Rats is Possibly Mediated by Adiponectin Expression

Hypoglycemia, as a direct result of the glucosuria is usually seen in patients with acute kidney injury hence glucose homeostasis is disturbed. The compensatory effect of adiponectin in the insulin deficient state is documented. We previously demonstrated that L-arginine enhances glucose transport mechanisms in renal-damaged rats. The current study was designed to investigate possible glucose handling synergy between L-arginine and adiponectin in Wistar rats induced with acute kidney injury. Twenty four rats weighing between 120g-150g were divided into 4 groups of six rats each. Group 1 (Control) had normal feed and water; Group 2 (Untreated) was induced with AKI and left untreated. Group 3 and 4 took 50mg/kg and 500mg/kg L-arginine respectively after AKI induction. Acute kidney injury was induced by intra-muscular injection of glycerol (50% solution, 8 ml/kg BW). Oral glucose tolerance test, insulin response test, serum creatinine test and adiponectin assay (ELISA) were carried out. Data was analysed using one way ANOVA and expressed as mean± standard error of mean (SEM) with p ≤ 0.05 considered as significant. L-arginine induced rapid insulin-like action which was effective after thirty minutes of oral glucose loading when compared the control group. Glucose uptake from the blood was also more effective and quicker in the L-arginine treated groups. Adiponectin was significantly expressed across the test groups when compared to the control group and there was insulin resistance in the untreated kidney injured rats 1 hour into the insulin response test. It may be concluded that L-arginine has a homeostatic influence on glucose handling in kidney-damaged rats possibly mediated by increased adiponectin expression.

High doses of catecholamines activate glucose transport in human adipocytes independently from adrenoceptor stimulation or vanadium addition.

BACKGROUNDWhen combined with vanadium salts, catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIMTo test whether catecholamines activate glucose transport in human adipocytes.METHODSThe uptake of 2-deoxyglucose (2-DG) was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery. Pharmacological approaches with amine oxidase inhibitors, adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline (also named epinephrine).RESULTSIn human adipocytes, 45-min incubation with 100 µmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin. This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium. Among various natural amines and adrenergic agonists tested, no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake. The effect of the catecholamines was not impaired by pargyline and semicarbazide, contrarily to that of benzylamine or methylamine, which are recognized substrates of semicarbazide-sensitive amine oxidase. Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone, and only the former was potentiated by vanadate. Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake. CONCLUSIONHigh doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes. At submillimolar doses, vanadium did not enhance this catecholamine activation of glucose transport. Consequently, this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.

Oral Supplementation with Benzylamine Delays the Onset of Diabetes in Obese and Diabetic db-/- Mice.

Substrates of semicarbazide-sensitive amine oxidase (SSAO) exert insulin-like actions in adipocytes. One of them, benzylamine (Bza) exhibits antihyperglycemic properties in several rodent models of diabetes. To further study the antidiabetic potential of this naturally occurring amine, a model of severe type 2 diabetes, the obese db-/- mouse, was subjected to oral Bza administration. To this end, db-/- mice and their lean littermates were treated at 4 weeks of age by adding 0.5% Bza in drinking water for seven weeks. Body mass, fat content, blood glucose and urinary glucose output were followed while adipocyte insulin responsiveness and gene expression were checked at the end of supplementation, together with aorta nitrites. Bza supplementation delayed the appearance of hyperglycemia, abolished polydypsia and glycosuria in obese/diabetic mice without any detectable effect in lean control, except for a reduction in food intake observed in both genotypes. The improvement of glucose homeostasis was observed in db-/- mice at the expense of increased fat deposition, especially in the subcutaneous white adipose tissue (SCWAT), without sign of worsened inflammation or insulin responsiveness and with lowered circulating triglycerides and uric acid, while NO bioavailability was increased in aorta. The higher capacity of SSAO in oxidizing Bza in SCWAT, found in the obese mice, was unaltered by Bza supplementation and likely involved in the activation of glucose utilization by adipocytes. We propose that Bza oxidation in tissues, which produces hydrogen peroxide mainly in SCWAT, facilitates insulin-independent glucose utilization. Bza could be considered as a potential agent for dietary supplementation aiming at preventing diabetic complications.

Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediated via adrenoceptor stimulation or monoamine oxidase activity.

BACKGROUNDBenzylamine and methylamine activate glucose uptake in adipocytes. For tyramine, this effect has even been extended to cardiomyocytes.AIMTo investigate the effects of catecholamines and other amines on glucose uptake.METHODSA screening compared 25 biogenic amines on 2-deoxyglucose (2-DG) uptake activation in rat adipocytes. Pharmacological approaches and transgenic mouse models were then used to decipher the mode of action of several hits.RESULTSIn rat adipocytes, insulin stimulation of 2-DG uptake was reproduced with catecholamines. 100 µmol/L or 1 mmol/L adrenaline, noradrenaline, dopamine and deoxyepinephrine, maximally activated hexose transport only when sodium orthovanadate was added at 100 µmol/L. Such activation was similar to that already reported for benzylamine, methylamine and tyramine, well-recognized substrates of semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase (MAO). Several, but not all, tested agonists of β-adrenoreceptors (β-ARs) also activated glucose transport while α-AR agonists were inactive. Lack of blockade by α- and β-AR antagonists indicated that catecholamine-induced 2-DG uptake was not mediated by AR stimulation. Adipocytes from mice lacking β1-, β2- and β3-ARs (triple KO) also responded to millimolar doses of adrenaline or noradrenaline by activating hexose transport in the presence of 100 µmol/L vanadate. The MAO blocker pargyline, and SSAO inhibitors did not block the effects of adrenaline or noradrenaline plus vanadate, which were blunted by antioxidants.CONCLUSIONCatecholamines exert unexpected insulin-like actions in adipocytes when combined with vanadium. For limiting insulin resistance by activating glucose consumption at least in fat stores, we propose that catecholamine derivatives combined with vanadium can generate novel complexes that may have low toxicity and promising anti-diabetic properties.

Obesity of mice lacking VAP-1/SSAO by Aoc3 gene deletion is reproduced in mice expressing a mutated vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity.

The product of Aoc3 gene is known as vascular adhesion protein-1 (VAP-1), a glycoprotein contributing to leukocyte extravasation and exhibiting semicarbazide-sensitive amine oxidase activity (SSAO). Regarding the immune functions of VAP-1/SSAO, it is known that mice bearing Aoc3 gene knock-out (AOC3KO) exhibit defects in leukocyte migration similar to those of mice expressing a mutated VAP-1 lacking functional SSAO activity (knock-in, AOC3KI). However, it has not been reported whether these models differ regarding other disturbances. Thus, we further compared endocrine-metabolic phenotypes of AOC3KO and AOC3KI mice to their respective control. Special attention was paid on adiposity, glucose and lipid handling, since VAP-1/SSAO is highly expressed in adipose tissue (AT). In both mouse lines, no tissue SSAO activity was found, while Aoc3 mRNA was absent in AOC3KO only. Although food consumption was unchanged, both AOC3KO and AOC3KI mice were heavier and fatter than their respective controls. Other alterations commonly found in adipocytes from both lines were loss of benzylamine insulin-like action with unchanged insulin lipogenic responsiveness and adiponectin expression. A similar downregulation of inflammatory markers (CD45, IL6) was found in AT. Glucose handling and liver mass remained unchanged, while circulating lipid profile was distinctly altered, with increased cholesterol in AOC3KO only. These results suggest that the lack of oxidase activity found in AOC3KI is sufficient to reproduce the metabolic disturbances observed in AOC3KO mice, save those related with cholesterol transport. Modulation of SSAO activity therefore constitutes a potential target for the treatment of cardiometabolic diseases, especially obesity when complicated by low-grade inflammation.

Royal Jelly: Chemistry, Storage and Bioactivities

Abstract Royal jelly (RJ) has been known for centuries, but in the last 5-6 decades its systematic production and consumption has increased. RJ is secreted by the hypopharyngeal and mandibular glands of worker honeybees (Apis mellifera). This thick and milky substance contains water, proteins, carbohydrates, lipids, minerals, vitamins and such bio-active compounds as acetylcholine, peptides, the hormones testosterone, progesterone, prolactin, estradiol, (hydroxydecanoic acid) (HAD), adenosine monophosphate (AMP)-N1Oxide, polyphenols, flavonoids and adenosine. Because of its bioactive compounds, RJ can be considered as a functional and nutraceutical food. The main goal of this review is to summarize and update its physicochemical properties, bio-active ingredients, storage stability and shelf life. The functional properties are antioxidative activity, insulin-like action, improvement against diabetes, liver protection, antitumoral action, neurotrophic action, antibiotic effect, anti-inflammatory action and wound healing, hypotensive effect and blood regulatory actions, anti-aging effect and skin protection, effects on the reproductive system and fertility and also fortifying, tonic action and immunomodulating and anti-alergic activity. RJ may cause allergic reactions, asthma and even fatal anaphylaxis in some humans. Therefore, RJ should be orally ingested as nutreaceutical agent or food-ingredient only after an allergy test.

Possible Therapeutic Role of Novel Vanadium Complexes in Diabetes MellitusAnimal Models

Diabetic mellitus is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period, diabetes can causes many complications. The trace element vanadium has unclear biological functions. Vanadate, an oxidized form of vanadium, appears to have an insulin-like action, the effect of vanadate on blood glucose was assessed in male Wistar rats after they were made diabetic with Streptozotocin (STZ). The animals were fasted overnight and a single intraperitoneal injection of a freshly prepared solution of STZ (55 mg/Kg b.wt) in 0.1 M cold citrate buffer (PH 4.5) was given to induce diabetes. The animals were allowed to access to 5 per cent glucose solution overnight, to prevent total hypoglycemia, induced by STZ by massive pancreatic insulin release. The animals were considered as diabetic, if their blood glucose values were above 250 mg/dL on the third day (72 hours) after STZ injection. The treatment was started on the fourth day after STZ injection and the day was considered as first day of treatment. The treatment was continued for 15 days. Diabetes causes disturbance in liver and kidney functions and causes hyperlipidemia also decreased the antioxidant activity; after the treatment with the two novel vanadium complexes , all functions of liver (Alanine transferase, Aspartate transferase and total protein) and kidney functions ( Creatinine and urea ) were improved. Also, lipid profile (total cholesterol and Triglycerides) level decreased and the activity of antioxidant enzymes (Superoxidedismutase, Glutathione peroxidase, Glutathione reductase and Malonodialdhyde) improved.

Naringenin and its Nano-formulations for Fatty Liver: Cellular Modes of Action and Clinical Perspective.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease mainly caused by high-fat diets and sudden feed changes, vitamin and energy deficiency, and inflammatory processes. Fatty liver leads to cirrhosis, hepatocellular carcinoma as well as liver failure. Lifestyle-modifying such as weight loss and a healthy diet have an inverse correlation with the risk of fatty liver. The promising effect of a diet rich in vegetables and fruits against fatty liver has been evidenced by several empirical studies focused on flavonoids. Among naturally occurring flavonoids, naringenin is one of the most important flavonoids which can be isolated from some edible fruits, especially citrus species. In the present review, we discuss the effects of naringenin and its nano-formulations against fatty liver disease and the proposed molecular mechanism of action. A large number of studies attributed to naringenin anti-inflammatory, antioxidant and insulin-like actions, as well as different types of effects on sex hormone metabolism and lipid metabolism. Naringenin-loaded nanoparticles have been used to solve the limited stability, solubility, bioavailability and pharmacological activity of naringenin and, consequently, to improve its therapeutic effects. Naringenin exerts diverse biological actions including the decrease of biomarkers of lipid peroxidation and protein carbonylation, increase of antioxidant defenses, scavenging of reactive oxygen species and modulation of signaling pathways related to fatty acid metabolism which can favor the oxidation of fatty acid, lower lipid accumulation in the liver and thereby prevent fatty liver.

Serum visfatin as predictive marker of cardiometabolic risk in women with polycystic ovary syndrome

Abstract Background Polycystic ovary syndrome (PCOS) is associated with a high risk of cardiovascular diseases (CVD). Visfatin is an adipocytokine with insulin-like action and it’s closely related to the amount of visceral fats. The objective of our study was to evaluate serum visfatin levels among women with PCOS. Also, to evaluate the association between serum visfatin and cardio-metabolic risk factors as well as clinic-morphological features of PCOS. Methods Case control study enrolled 120 women diagnosed with PCOS and 80 healthy control women. PCOS cases were stratified according to their fasting plasma glucose (FPG) into three subgroups: those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Serum visfatin levels (ng/ml) were assessed by ELISA. Results Our results revealed higher values of cardio-metabolic risks; total cholesterol, triglycerides, LDL cholesterol, high-sensitivity C-reactive protein (hs-CRP), fasting serum insulin (FSI), HbA1c, HOMA-IR, and FPG in PCOS compared to healthy women. In addition, compared with healthy women (28.66 ± 10.63), PCOS patients (87.98 ± 17.96) had significantly higher levels of serum visfatin. Among PCOS group, T2DM patients (119.59 ± 14.52) had significantly higher levels of serum visfatin compared to IGT (81.03 ± 15.81) and NGT (85.09 ± 11.01). Receiver operating characteristic analyses revealed that serum visfatin was a useful biomarker discriminating PCOS from control, the AUC was 0.989 with sensitivity = 99.2%, specificity = 99.8%, Additionally, the sensitivities and the specificities of visfatin in differentiating T2DM from NGT were (93.3% and 98.2%). Stepwise multiple linear regression analysis revealed that androstenedione, LH, free androgen index and ovarian volume were the main predictors of visfatin levels among PCOS. Conclusion Serum visfatin levels could discriminate PCOS from healthy control and T2DM from NGT PCOS women. Moreover, vesfatin was positive correlated to cardio-metabolic risk factors. Interestingly, the sensitivity and specificity power of vesfatin were high. Thus, it could be early predicting of cardio-metabolic risks among PCOS women and might be useful in therapeutic intervention in future.

Mechanism of insulin-like effect of chromium(III) ions on glucose uptake in C2C12 mouse myotubes involves ROS formation

Chromium is considered a trace element which improves glucose tolerance, but mechanism accounting for this insulin-like action is not recognized. The main purpose of this study was to examine the role of reactive oxygen species (ROS) in chromium and insulin stimulated glucose transport using antioxidants. Effect of chromium ions on phosphatases, enzymes involved in inhibition of insulin signaling was also investigated. Experiments were performed in vitro on C2C12 mouse myotubes. ROS level was measured with the use of confocal microscope and 2’,7’ dichlorodihydrofluorescein diacetate (DCFH-DA). Glucose metabolism was assayed by the measurement of 2-[3H]-deoxyglucose uptake. Cr3+ ions and insulin treatment caused significant increase of ROS formation and also stimulated glucose uptake in C2C12 cells in concentration dependent manner. Antioxidants (L-ascorbic acid and N-acetyl cysteine 100μM) and DPI (diphenyleneiodonium-NADPH oxidase inhibitor, 10μM) abolished insulin- and Cr-inducted glucose transport. Our results confirm the hypothesis that the ROS are integral part of insulin signaling pathway and that the insulin mimetic effect of Cr3+ ions depends on the antioxidant status of the cells. Surprisingly, chromium treatment resulted in increased activity of membrane phosphatases.

Tyramine activates lipid accumulation in rat adipocytes: influences of <em>in vitro</em> and <em>in vivo</em> administration

Tyramine is naturally occurring in foods. This biogenic amine is known to induce hypertension, especially when ingested by individuals treated by irreversible inhibitors of monoamine oxidases (MAO). However, in animals, tyramine is also an agonist for trace amine-associated receptors and substrate of semicarbazide-sensitive amine oxidases (SSAO). Though tyramine can alter aminergic transmission by various mechanisms, it was recently reported that prolonged tyramine supplementation does not deteriorate glucose tolerance and does not cause adverse cardiovascular effects in mice. Since previous studies have described insulin-like effects of tyramine in fat cells from diabetic rats, we have further tested tyramine in vitro and in vivo actions on fattening. To this aim, antilipolytic and lipogenic responses to insulin and tyramine were first compared in rat adipocytes while tyramine oxidation was compared in adipose and intestinal tissues. Then, effects of repeated intraperitoneal injections of tyramine (17 µmol/kg/day) on adiposity and on adipocyte functions were studied in young and mature rats. Millimolar doses of tyramine inhibited glycerol release by adipocytes with a maximal antilipolytic effect comparable to that of insulin. Repeated tyramine administration enhanced fat deposition in epididymal white adipose tissue, irrespective of the age of treated rats. This effect was not accompanied by desensitization to lipogenic activation by insulin, tyramine or hydrogen peroxide. Lastly, tyramine was more readily oxidized in adipose than in intestinal tissues when enzymatic activity was expressed per mg of protein. Moreoever, MAO mostly contributed to oxidative deamination in gut while SSAO was predominant in fat. Thus, both short-term and prolonged effects of tyramine were evidencing somewhat insulin-like actions in adipose tissue and led to reconsider the risk/benefit ratio of the dietary intake of this amine.

Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells.

AIMTo assess in rodent and human adipocytes the antilipolytic capacity of hexaquis(benzylammonium) decavanadate (B6V10), previously shown to exert antidiabetic effects in rodent models, such as lowering free fatty acids (FFA) and glucose circulating levels.METHODSAdipose tissue (AT) samples were obtained after informed consent from overweight women undergoing plastic surgery. Comparison of the effects of B6V10 and reference antilipolytic agents (insulin, benzylamine, vanadate) on the lipolytic activity was performed on adipocytes freshly isolated from rat, mouse and human AT. Glycerol release was measured using colorimetric assay as an index of lipolytic activity. The influence of B6V10 and reference agents on glucose transport into human fat cells was determined using the radiolabelled 2-deoxyglucose uptake assay.RESULTSIn all the species studied, B6V10 exhibited a dose-dependent inhibition of adipocyte lipolysis when triglyceride breakdown was moderately enhanced by β-adrenergic receptor stimulation. B6V10 exerted on human adipocyte a maximal lipolysis inhibition of glycerol release that was stronger than that elicited by insulin. However, B6V10 did not inhibit basal and maximally stimulated lipolysis. When incubated at dose ≥ 10 μmol/L, B6V10 stimulated by twofold the glucose uptake in human fat cells, but - similarly to benzylamine - without reaching the maximal effect of insulin, while it reproduced one-half of the insulin-stimulation of lipogenesis in mouse fat cells.CONCLUSIONB6V10 exerts insulin-like actions in adipocytes, including lipolysis inhibition and glucose transport activation. B6V10 may be useful in limiting lipotoxicity related to obesity and insulin resistance.

Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions

d-chiro-inositol (DCI, 1) evokes therapeutic actions in diabetes and insulin resistance but has sub-optimal pharmacokinetic profiles. To investigate what positions on the DCI cyclohexanol ring may be amenable to modification to improve pharmaceutical formulations, a series of analogues based on DCI were synthesised. These compounds were then evaluated for their ability to stimulate glucose transport using 3T3-L1 adipocytes as a model system. Positional analyses indicate that the hydroxyl group at position 1 is not essential for activity and can be modified without affecting glucose uptake. Removal of the hydroxyl at position 3 also had minimal effect on activity but this group is sensitive to modification. By comparison, the oxygen at position 2 is crucial to the potency of DCI, although this group can withstand modification without fundamentally affecting activity. These data reveal that positions 1 and 2 on the cyclohexanol ring of DCI offer further scope for modification to develop DCI analogues with desirable pharmacokinetic profiles for the potential treatment of metabolic disease.

Association of Serum Selenium, Zinc and Magnesium Levels with Glycaemic Indices and Insulin Resistance in Pre-diabetes: a Cross-Sectional Study from South India.

A growing understanding of antioxidant mechanisms and insulin-like actions of trace elements selenium and zinc has rekindled researchers' interest towards their role in diabetes mellitus, nutritional management of which concentrates predominantly on macronutrient intake. However, selenium studies limiting largely to diabetes have yielded inconsistent results with sparse knowledge in the pre-diabetes population. This hospital-based cross-sectional study screened 300 people who came to the institutional hospital laboratory with fasting plasma glucose and glycosylated haemoglobin requisition over a period of 6months. Thirty-five pre-diabetes subjects aged 25-45years and 35 age-matched healthy controls were selected as per inclusion criteria and clinical history. Serum selenium was estimated by inductively coupled plasma-mass spectrometry, zinc and magnesium by colorimetric end-point methods and insulin by enzyme-linked immunosorbent assay, and insulin resistance was calculated using a homeostasis model assessment (HOMA) 2 calculator. Data analysis was done using SPSS ver. 16 employing an independent sample t test for intergroup comparison of means and Pearson's correlation for correlation analysis. Serum mineral levels in the pre-diabetes group (selenium 63.01±17.6μg/L, zinc 55.78±13.49μg/dL, magnesium 1.37±0.38mg/dL) were significantly reduced (p<0.05) in comparison to the healthy controls (selenium 90.98±15.81μg/L, zinc 94.53±15.41μg/dL, magnesium 2.12±0.22mg/dL). A significant negative correlation was seen with glycaemic indices and insulin resistance. This study conducted in pre-diabetes subjects highlights a considerable deficiency of serum selenium, zinc and magnesium observed at a much earlier pre-clinical phase. This coupled with the evidence of a strong inverse association with glycaemic indices and insulin resistance postulates the role of mineral alterations in the pathophysiology of hyperglycaemia and insulin resistance.

ANTE-MORTEM FORMATION OF THE QUALITATIVE CHARACTERISTICS OF ENVIRONMENTALLY FRIENDLY MEAT RAW MATERIAL BY INTENSIFICATION OF THE MECHANISMS OF THE METABOLIC PROCESSES IN GILTS

Abstract In order to reduce the time of feeding, increase the intensity of weight gain without hormones, antibiotics, anabolic drugs, as well as to obtain high-quality meat with marble structure, the authors studied the influence of ovarioectomy on the intensification of the metabolic processes in gilts. The experiments were carried out in the FGUP “Mummovskoe” – the educational experimental enterprise of the Russian State Agrarian University - Moscow Timiryazev Agricultural Academy (RSAU – MAA named after K.A. Timiryazev), in the Atkarsky district of the Saratov region. Two groups of Duroc gilts (10 animals each) raised under the same conditions were studied. As a result of the experiment, the influence of ovariectomy on the level of insulinlike growth factor-1 (IGF-1) and indicators of metabolic processes in gilts were established. It is confirmed that stimulation of the the somatotropin/insulin-like growth factor (ST-IGF) system along with hereditary factors and the characteristics of feeding contributes to the development of muscle tissue. Stimulation of ST secretion with insulin-like growth factor facilitates the development of muscle tissue. An increase in IGF-1 level leads to the development of new muscle fibers and muscle hyperplasia. After surgery, the major factors of changes in meat and feeding indicators in gilts were the rise in the metabolic activity of muscle tissue and fat metabolism, enhancement of production of IGF-1, which has insulin-like action and ensures activation of the processes of cell proliferation and differentiation. Increase in IGF-1 level had a positive impact on meat productivity, chemical and biochemical composition of pork. Simultaneous triggering of the systemic catabolic and local anabolic reactions in gilts after ovariectomy contributed to obtaining higher nutritional value of meat.

Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro. Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24h with 0.5mM creatine (CR), CR and 20μg/mL fenugreek seed extract (CR+FEN), CR and 100nM insulin (CR+INS), and CR+INS+FEN (n=6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined. Compared to control (CON), CR+INS+FEN increased total creatine content after 4h (P<0.05), whereas all conditions increased SLC6A8 protein expression above CON at this time (P<0.05). Changes in insulin signaling were demonstrated via increases in AktThr308 phosphorylation, with CR+INS>CON and CR at 1h (P<0.05) and with CR+INS+FEN>CON, CR, and CR+INS at 4h (P<0.05). In contrast, no changes in PKCζ/λ or GLUT4 phosphorylation were detected. Fenugreek, when combined with insulin, modulates creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.