Insulin-like Activity Research Articles

Dietary sucrose determines the regulatory activity of lithium on gene expression and lifespan in Drosophila melanogaster.

The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly Drosophila melanogaster. It is noteworthy that lithium is attributed with insulin-like activity as it stimulates protein kinase B/Akt and suppresses the activity of glycogen synthase kinase-3 (GSK-3). However, its interaction with dietary sugar has largely remained unexplored. Therefore, we investigated the effects of lithium supplementation on known lithium-sensitive parameters in fruit flies, such as lifespan, body composition, GSK-3 phosphorylation, and the transcriptome, while varying the dietary sugar concentration. For all these parameters, we observed that the efficacy of lithium was significantly influenced by the sucrose content in the diet. Overall, we found that lithium was most effective in enhancing longevity and altering body composition when added to a low-sucrose diet. Whole-body RNA sequencing revealed a remarkably similar transcriptional response when either increasing dietary sucrose from 1% to 10% or adding 1 mM LiCl to a 1% sucrose diet, characterized by a substantial overlap of nearly 500 differentially expressed genes. Hence, dietary sugar supply is suggested as a key factor in understanding lithium bioactivity, which could hold relevance for its therapeutic applications.

Ameliorative Effect of a Vanadium-thiosemicarbazone Complex on Oxidative Stress in Stomach Tissue of Experimental Diabetic Rats

Recently, we have shown that oral administrations of an oxidovanadium (IV) complex, VOL, with tetradentate thiosemicarbazone ligand normalizes hyperglycemia of streptozotocin-induced diabetic rats (STZ-rats). For the development of vanadium compounds that exhibit insulin-like behavior, it is essential to know some of the pharmacokinetic properties of these complexes. The goal of the current research is to examine the healing effect of new sythesed VOL complex on the oxidative stress parameters of diabetic stomac tissue. Rats used in the experiments were divided as control, VOL+control, diabetic and diabetic+VOL. The rats were sacrificed after 12 days of the experimental period. The levels of glutathione, lipid peroxidation, non-enzymatic glycosylation, advanced oxidized protein products levels and the activities of some enzymes were measured in stomach tissue of all the experimental animals. Although VOL treatment to diabetic rats increased the stomach glutathione levels; lipid peroxidation, non-enzymatic glycosylation and advanced oxidized protein products levels were decreased. Also, the activities of catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and carbonic anhydrase were increased in VOL treated diabetic group. Whereas, lactate dehydrogenase and xanthine oxidase activities were decreased. According to the obtained outcomes, it can be said that VOL treatment has a healing effect on the stomach tissue of diabetic rats. This effect provided by VOL is most likely due to the insulin-like and antioxidant activity of the complex. In conclusion, we can say that VOL may be a suitable candidate for diabetes treatment.

SAT141 A Case Of Non-islet Cell Tumor Hypoglycemia Which Was Ameliorated By Pazopanib Treatment

Abstract Disclosure: N. Yamamoto: None. M. Yamamoto: None. N. Kiyota: None. Y. Inaba: None. K. Kanie: None. S. Urai: None. M. Suzuki: None. Y. Sasaki: None. Y. Oi: None. Y. Tsujimoto: None. Y. Motomura: None. Y. Ohmachi: None. H. Bando: None. G. Iguchi: None. M. Nagao: None. I. Fukuda: None. H. Fukuoka: None. W. Ogawa: None. Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by insulin-like growth factor II (IGF-II) hypersecretion from the tumors. It is characterized by incompletely processed big IGF-II with potent insulin-like activity. We present a case of NICTH complicated with solitary fibrous tumor (SFT) which was ameliorated with the administration of pazopanib, a multi-targeted tyrosine kinase inhibitor. Clinical Case: A 57-year-old man went into a coma and was hospitalized. His plasma glucose levels were 26 mg/dL, and he regained consciousness after glucose administration, leading to a diagnosis of hypoglycemic coma. Moreover, a contrast-enhanced CT scan showed multiple tumors in his liver and right kidney. He was referred to our hospital for further management. After 5 hours of fasting, he had a cold sweat, and his plasma glucose levels dropped to 32 mg/dL with suppressed serum insulin levels of 0.2 U/mL. Serum 3-hydroxybutyrate levels were as low as 21 μmol/L, and plasma glucose levels increased to 83 mg/dL after glucagon administration, suggesting an agent mimicking insulin. Percutaneous liver biopsy was performed, and the tumors were diagnosed with SFT. Immunoblotting for his serum showed big IGF-II, leading to a diagnosis of NICTH, and hypoglycemia due to hypersecretion of IGF-II. Due to multiple metastases, surgery was not indicated and pazopanib was administered. Hypoglycemia during the night was prevented by glucose infusion through the central venous port, and he was discharged. Three months later, when he was re-hospitalized for thrombophlebitis of the right jugular vein, hypoglycemia did not occur even after 10 hours of fasting and CT scan showed the necrotic change of the tumor. Two weeks later of pazopanib discontinuation due to the thrombogenic adverse effect, hypoglycemia recurred accompanied by the tumor enlargement. When the anticoagulation therapy regressed the thrombosis and pazopanib was re-administered, hypoglycemia improved reproducibly and remained stable for more than 2 years although the tumor showed gradual progression. Conclusion: This is the first case in which pazopanib was effective in suppressing NICTH associated with SFT. Presentation: Saturday, June 17, 2023

In Vitro Micropropagation of Endangered Achillea fragrantissima Forssk. Combined with Enhancement of Its Antihyperglycemic Activity

Achillea fragrantissima Forssk. (Family: Asteraceae) has been used as a natural remedy in the Arabian region for its antihyperglycemic activity. As a result of the intensive demand for this plant in folk medicinal uses, its scarcity has become problematic. This study has explored methods that produce an efficient in vitro culture protocol for the conservation of this plant as well as the enhancement of its hypoglycemic activity. A. fragrantissima cultures on Murashige and Skoog (MS) medium supplemented with 3.6 µM/L of 6-benzyl aminopurine (BAP) for a two month period resulted in maximum in vitro shoot proliferation (12.33 shoots/explant) while MS medium supplemented with 2.4 µM/L 1-naphthalene acetic acid (NAA) provided maximum in vitro adventitious root formation (2.46 roots/shoot tip explant). Callus induction was favored by leaf explants cultured on MS medium and supplemented with 3 µM/L BAP and 3 µM/L IAA media in dark conditions. Further in vivo study of some selected feedings determined that the best hypoglycemic activity was obtained in either indole-3-butyric acid (IBA)-fed plants (24%) or NAA-fed plants (22%). Both treatments enhanced insulin-like activity in STZ-treated diabetic Sprague-Dawley rats when compared with the wild plant (10%). Moreover, the IBA-fed plants showed significant antioxidant activity while the NAA-fed plants inhibited salivary alpha amylase. The framework of this study provides in vitro culture methods that can sustain the cultivation of this over-exploited A. fragrantissima plant as well as increase its antioxidant and insulin-like activities.

The Antioxidant, Anti-Inflammatory and Immunomodulatory Effects of Camel Milk

Camel milk (CM) has been found to have several health benefits, including antiviral, antibacterial, anti-tumor, anti-fungal, antioxidant, hypoglycaemic and anti-cancer activities. In addition, CM can counter signs of aging and may be a useful naturopathic treatment for autoimmune diseases. The composition of CM varies with geographic origin, feeding conditions, seasonal and physiological changes, genetics and camel health status. In the present review, we collate the diverse scientific literature studying antioxidant, anti-inflammatory and immunomodulatory effects of CM and its bioactive compounds. The databases Scopus, PubMed, and Web of Science were searched until the end of September 2021 using the keywords: camel milk, antioxidant, anti-inflammatory, immunomodulatory. The anti-inflammatory mechanism of CM in various inflammatory disorders was consistently reported to be through modulating inflammatory cells and mediators. The common anti-inflammatory bioactive components of CM seem to be lactoferrin. The antioxidant effects of α-lactalbumin, β-caseins and vitamin C of CM work by reducing or inhibiting the production of reactive oxygen species (ROS), hydroxyl radicals, nitric oxide (NO), superoxide anions and peroxyl radicals, likely alleviating oxidative stress. Higher levels of protective proteins such as lysozyme, IgG and secretory IgA compared to cow’s milk, and insulin-like protein activity of CM on ß cells appear to be responsible for the immunomodulatory properties of CM. The evidence indicates that CM and its bioactive components has the potential to be a therapeutic value for diseases that are caused by inflammation, oxidative stress and/or immune-dysregulation.

Syntheses, spectral characterization and antidiabetic activities of oxidovanadium(V) complexes with bi-and tridentate ligands

Four new oxidovanadium(V) complexes [VO(L 1 )(Mol)] ( 1 ), [VO(L 2 )(Mol)] ( 2 ), [VO(L 3 )(Mol)] ( 3 ) and [VO(L 4 )(Mol)] ( 4 ) (where L 1 -L 4 = aroylhydrazones and Mol = maltol) have been synthesized with different ligands. The complexes have been characterized using microanalysis, spectral fab mass, UV-visible, electrochemical (cyclic voltammetry and differential pulse voltammetry), density functional theory calculations have been performed to predict the optimized geometry, global reactivity parameters and electron density. In these complexes, the d-d absorption band is not observed as being d 0 vanadium centres in these complexes. The electrochemical behaviour of these complexes are explored by cyclic voltammetry and differential pulse voltammetry (DPV). All complexes exhibit one electron transfer i.e., reduction of vanadium(V) to vanadium(IV). These complexes are screened for in vitro α-glucosidase and α-amylase inhibition study. Complex 3 has an interesting insulin-like activity.

PENGARUH REBUSAN DAUN BINAHONG (ANREDERA CARDIFOLIA) TERHADAP KADAR GULA DARAH PADA LANSIA DM TIPE II DI PUSKESMAS KOTA DATAR

Diabetes mellitus (DM) is a metabolic disease that occurs due to damage to insulin secretion and insulin action which can be measured by looking at blood glucose levels. Binahong leaves contain saponins which have insulin-like activity, can inhibit lipolysis, and increase glucose uptake by adipose cells. This study aims to determine the effect of binahong leaf decoction on blood sugar levels in the elderly with type II diabetes mellitus at Kota Datar Public Health Center. Hamparan Perak Sub distict. This study is a quasi-experimental study with a pre and post test only one group design on 22 elderly people at Kota Datar Public Health Center, Hamparan Perak Sub Distict with binahong leaf decoction and the intervention is carried out for 14 days. The paired-test method is used to analyze the different tests for the effect of binahong leaf decoction on blood sugar levels in the elderly before and after the intervention. The results show that the average blood sugar level of the elderly with type II diabetes before being given binahong leaf decoction iss 182.41 mg / dl with an SD value of 31,304, and the lowest blood sugar level is 89 mg / dl and the highest is 201 mg / dl. The average of blood sugar level in the elderly with type II diabetes mellitus after being given binahong leaf decoction is 151.82 with SD value of 31.304, and the lowest blood sugar level is 89 mg / dl and the highest is 201 mg / dl. There is a significant difference in blood sugar levels in the elderly with type II diabetes mellitus at Kota Datar Public Health Center, Hamparan Perak Sub distict with P value = 0.001 (α <0.05). There is a decrease in blood sugar levels in the elderly with type II diabetes. It is Concluded that giving binahong leaf stew can reduce blood sugar levels in the elderly with type II diabetes mellitus at Kota Datar Community Health Center, Hamparan Perak Sub distict.

In-Silico Analysis of Procyanidin Type-A Extracted From Cinnamon for Diabetes Mellitus Type 2 Treatment

Type 2 diabetes mellitus (T2DM) is the most common disease in developing countries. People with type-2 diabetes are at high risk of complications leading to disability and premature death. Procyanidin compounds in cinnamon have an insulin-like activity that can regulate normal blood sugar levels. This research aimed to investigate the interaction between α-glucosidase and α-amylase with procyanidin A and their potential for diabetes treatment therapy. Data mining receptor was downloaded from RCSB PDB and ligands from PubChem. Drug likeness properties were evaluated using SwissADME, while toxicity analysis was assessed using metatox. Molecular docking between α-glucosidase and α-amylase with procyanidin A was performed using HEX 8.0.0 and was visualized by Discovery Studio. Procyanidin A showed interaction with α-glucosidase by non-bonds interaction, including hydrogen, hydrostatic and hydrophobic bonds, while procyanidin A and α-amylase formed hydrogen and hydrophobic bonds. Procyanidin A is an alternative treatment for T2DM with a variety of supportive chemical bonds. Procyanidin A has an excellent ability to inhibit activity α-glucosidase and α-amylase in the process of breaking down glucose in the intestines.

Anticancer effect of sodium metavanadate on murine breast cancer both in vitro and in vivo.

Sodium metavanadate (NaVO3) exhibits important physiological effects including insulin-like, chemoprevention and anticancer activity. However, the effects of NaVO3 on breast cancer and underlying mechanisms are still unclear. In this study, our results revealed that NaVO3 was able to inhibit proliferation of murine breast cancer cells 4T1 with IC50 value of 8.19μM and 1.92μM at 24h and 48h, respectively. The mechanisms underlying the inhibition activity were that NaVO3 could increase reactive oxygen species (ROS) level in a concentration-dependent way, arrest cells at G2/M phase, diminish the mitochondrial membrane potential (MMP), finally promote the progress of apoptosis. Furthermore, NaVO3 also exhibited a dose-dependent anticancer activity in breast cancer-bearing mice that led to the shrinkage of tumor volume (about 50%), lower microvessel density, less propagating cells and more apoptotic cells in vivo, as compared to the saline group. Therefore, NaVO3 may act as a potential chemotherapeutic agent in breast cancer treatment.

Selection of Small Molecules that Bind to and Activate the Insulin Receptor from a DNA-Encoded Library of Natural Products.

SummaryAlthough insulin is a life-saving medicine, administration by daily injection remains problematic. Our goal was to exploit the power of DNA-encoded libraries to identify molecules with insulin-like activity but with the potential to be developed as oral drugs. Our strategy involved using a 104-member DNA-encoded library containing 160 Traditional Chinese Medicines (nDEL) to identify molecules that bind to and activate the insulin receptor. Importantly, we used the natural ligand, insulin, to liberate bound molecules. Using this selection method on our relatively small, but highly diverse, nDEL yielded a molecule capable of both binding to and activating the insulin receptor. Chemical analysis showed this molecule to be a polycyclic analog of the guanidine metformin, a known drug used to treat diabetes. By using our protocol with other, even larger, DELs we can expect to identify additional organic molecules capable of binding to and activating the insulin receptor.

The Effect of Inorganic and Organic Zinc Supplementation on Growth Performance, Mineral Profile and Gene Expression Pattern of GLUT1 in Malabari Kids.

The objective of this experiment was to study and compare the effects of dietary supplementation of organic and inorganic zinc (Zn) on growth performance, nutrient utilisation and gene expression pattern of glucose transporter protein in peripheral blood mononuclear cells (PBMC) in Malabari kids. Fifteen, 3-4-month-old goat kids were divided into three groups uniformly by using completely randomised design (CRD). Group G1 was fed on basal diet as per NRC requirement, and G2 and G3 were fed on basal diet + 40ppm Zn as inorganic zinc sulphate (ZnSO4) and 40ppm Zn as organic Zn methionine, respectively, for a period of 91days. Supplementation of inorganic and organic Zn had no significant effect on dry matter (DM) intake. The digestibility of crude protein (CP), ether extract (EE), neutral detergent fibre (NDF), hemicellulose and cellulose was significantly more in the organic Zn-supplemented group. The average daily gain and feed:gain ratio were significantly (p < 0.05) better in group G3 in comparison to G1 and G2, while the nitrogen retention was found to be (p < 0.01) higher in group G3 than in group G1. Zinc balance was found to be significantly (p < 0.01) increased in both supplemented groups with respect to unsupplemented group G1. The blood glucose level was (p < 0.01) lower in group G3 compared to group G1 suggesting the insulin-like activity of Zn. Serum Zn concentration was significantly (p < 0.01) increased in both Zn-supplemented groups. There was a significant (p < 0.05) rise in glucose transporter GLUT1 expression in groups G2 and G3 when compared to control group G1. Moreover, GLUT1 expression was found to be higher (p < 0.05) in group G3 as against the animals of group G2. Lowered blood glucose level might have stimulated more glucose transporter GLUT1 expression in PBMC. Organic Zn supplemented at 40ppm level resulted in better growth performance, nutrient digestibility and nitrogen as well as Zn retention in goat kids. There was better absorption, and hence, less amount of Zn got excreted in the organic Zn-supplemented group.

Receptor-mediated attenuation of insulin-like growth factor-1 activity by galactose-1-phosphate in neonate skin fibroblast cultures: Galactosemia pathogenesis.

The pathogenesis of classical galactosemia, a rare metabolic disorder associated with developmental complications in neonates and children due to inherited deficiency of galactose-1-phosphate (Gal-1-P) uridylyltransferase (GALT), is known to be mediated by elevated Gal-1-P levels and involves a cascade of cytokines, reactive oxygen species (ROS) and growth factors. To examine ex vivo the effect of Gal-1-P on the mitogenic activity of different growth factors, particularly insulin-like growth factor-1 (IGF-1), known to regulate growth and development from the fetal stage to adulthood. Fibroblasts derived from the foreskin of 3-8-day-old healthy neonates were cultured for 1-14 days with 0-20 mM galactose or 0-10 mM Gal-1-P and then stimulated with 5% fetal bovine serum (FBS) or 50 ng/mL of platelet-derived growth factor (PDGF) or fibroblast growth factor (FGF) or IGF-1 for 24 h. DNA synthesis was measured and protein expression of PDGFR, FGFR and IGF-1R was assessed with western blotting. Supra-physiological concentrations of galactose significantly decreased FBSand IGF-1-induced BrdU incorporation. The presence of Gal-1-P (5-10 mM) in culture medium for 7-14 days significantly (p < 0.01) decreased IGF-1-, PDGFand FBS-stimulated DNA synthesis. While treatment with Gal-1-P selectively and significantly (p < 0.01) reduced the protein expression of IGF-1 receptor, galactose treatment did not have any marked effect on examined growth factor receptors. This study demonstrates that Gal-1-P impairs IGF-1 activity through IGF-1-receptor impairment, thereby providing a new insight into the molecular mechanisms of galactosemia pathogenesis.

Assessing the Immunomodulatory Activity of Ethanol Extract of Sambucus javanica Berries and Leaves in Chloramphenicol-Induced Aplastic Anemia Mouse Model.

Aplastic anemia, life-threatened disease, is a hematologic disorder characterised by bone marrow hypoplasia. Multiple modalities such as bone marrow transplantation and immunosuppression treatment have been proposed to ameliorate this entity, however it remains ineffective. Sambucus, a group of herb plants, possesses a broad spectrum of medicinal properties such as antioxidant, insulin-like activity, anticancer and antiviral. However, the study about its activity toward aplastic anemia incidence is based on limited data. Thus, the research aim of this study was to evaluate the immunomodulatory activities of Sambucus javanica in chloramphenicol-induced anemia aplastic mouse model. In this present study, BALB/c mice were administrated with chloramphenicol (CMP) to induce aplastic anemia then followed by S. javanica extracts treatment. Additionally, cellular and molecular aspects were evaluated by flow cytometry and Hematoxylin-Eosin staining. Further analysis showed that S. javanica extracts could promote the population number of regulatory T-cells and naive cytotoxic T-cells. Moreover, those extract also reduced the inflammation and necrotic incidence in CMP-induced mouse aplastic anemia model. Together, these results suggest that S. javanica has therapeutically effect to aplastic anemia by altering the immune system as an immunomodulatory agent.

Expression of the Biologically Active Insulin Analog SCI-57 in Nicotiana Benthamiana.

Diabetes mellitus is a growing problem worldwide; however, only 23% of low-income countries have access to insulin, and ironically it costs higher in such countries than high-income ones. Therefore, new strategies for insulin and insulin analogs production are urgently required to improve low-cost access to therapeutic products, so as to contain the diabetes epidemic. SCI-57 is an insulin analog with a greater affinity for the insulin receptor and lower thermal degradation than native insulin. It also shows native mitogenicity and insulin-like biological activity. In this work, SCI-57 was transiently expressed in the Nicotiana benthamiana (Nb) plant, and we also evaluated some of its relevant biological effects. An expression plasmid was engineered to translate an N-terminal ubiquitin and C-terminal endoplasmic reticulum-targeting signal KDEL, in order to increase protein expression and stability. Likewise, the effect of co-expression of influenza M2 ion channel (M2) on the expression of insulin analog SCI-57 (SCI-57/M2) was evaluated. Although using M2 increases yield, it tends to alter the SCI-57 amino acid sequence, possibly promoting the formation of oligomers. Purification of SCI-57 was achieved by FPLC cation exchange and ultrafiltration of N. benthamiana leaf extract (NLE). SCI-57 exerts its anti-diabetic properties by stimulating glucose uptake in adipocytes, without affecting the lipid accumulation process. Expression of the insulin analog in agroinfiltrated plants was confirmed by SDS-PAGE, RP-HPLC, and MS. Proteome changes related to the expression of heterologous proteins on N. benthamiana were not observed; up-regulated proteins were related to the agroinfiltration process. Our results demonstrate the potential for producing a biologically active insulin analog, SCI-57, by transient expression in Nb.

A Genome-Wide Association Study of Sprint Performance in Elite Youth Football Players

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leońska-Duniec, A, Pająk, B, Chycki, J, Moska, W, Lulińska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cięszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.

Synthesis, crystal structures and insulin-like activity of three new oxidovanadium(V) complexes with aroylhydrazone ligand

Three new oxidovanadium(V) complexes were designed, synthesized and characterized by C, H, N elemental analysis, single crystal X-ray diffraction，UV/Vis and IR spectra. Complex 1: [VOL1X] (H2L1 = (E)-N′-(2-hydroxybenzylidene)-3-methbenzohydrazide, HX = ethylmaltol = 2-ethyl-3-hydroxy-4-pyrone), Complex 2: [VOL2(CH3O)(CH3OH)], (H2L2 = C16H16N2O4 = (E)-N′-(2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide, CH3OH = methanol), Complex 3: [VOL3X] (H2L3 = (E)-N′-(3-ethoxy-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide). The insulin-like activity of the three complexes was tested. Both normal and streptozotocin (STZ)-diabetic mice were administered intragastrically for two weeks. It was found that the complexes at doses of 10.0 and 5.0 mg V·kg−1 can significantly decrease the blood glucose level in STZ-diabetic mice, and the blood glucose level in the treated normal mice was not altered. The lesions of kidney and liver caused by diabetes have varying degrees of improvement.

Biochemical relevance of Cr(III) complexes of isoniazid: synthesis, characterization, DFT, antibacterial screening, antioxidant activity and glucose-lowering effect in STZ-induced diabetic rats

Molecular mechanism suggests that the incorporation of an antioxidant organic moiety to chromium will be a sound strategy for the synthesis of safer and more effective hypoglycemic compounds. Two Schiff base ligands were derived by condensation of isonicotinyl hydrazide with salicylaldehyde/o-hydroxyacetophenone which further yield four novel chromium(III) complexes of types [Cr(L)Cl2(H2O)] and [Cr(L)2]Cl. The ligands and complexes were characterized by analytical and spectroscopic techniques. DFT study at the basic set B3LYP and TD-SCF/6-311-G level was employed to confirm the geometry of the investigated compounds. Ligands were tested for their antioxidant activity and exhibited good antioxidant activity. Assessment of insulin-like activity of the complexes was initially performed in vitro by measuring the inhibition of α-amylase. The complex with highest in vitro activity was investigated for in vivo antidiabetic activity on the model of STZ-induced diabetic rats, which demonstrated that complex 4 significantly lowers the blood glucose level in rats. Toxicity level and antioxidant activity of the complex were also tested, which exhibit good tolerance level and antioxidant activity. Histological analysis of the pancreas of animals under investigation reveals the good condition of the pancreas treated with the complex. Ligands and complexes were also tested for antibacterial activity against Escherichia coli.

Topical application of Cinnamomum hydroethanolic extract improves wound healing by enhancing re-epithelialization and keratin biosynthesis in streptozotocin-induced diabetic mice

Context: Cinnamomum verum J. Presl. (Lauraceae) has a high number of polyphenols with insulin-like activity, increases glucose utilization in animal muscle, and might be beneficial for diabetic patients.Objective: This study evaluated the effectiveness of an ointment prepared from Cinnamomum verum hydroethanolic extract on wound healing in diabetic mice.Materials and methods: A total of 54 male BALB/c mice were divided into three groups: (1) diabetic non-treated group mice that were treated with soft yellow paraffin, (2 and 3) mice that were treated with 5 and 10% C. verum. Two circular full-thickness excisional wounds were created in each mouse, and the trial lasted for 16 d following induction of the wound. Further evaluation was made on the wound contraction ratio, histopathology parameters and mRNA levels of cyclin D1, insulin-like growth factor 1 (IGF-1), glucose transporter-1 (GLUT-1), total antioxidant capacity, and malondialdehyde of granulation tissue contents. HPLC apparatus was utilized to identify the compounds.Results: The HPLC data for cinnamon hydroethanolic extract identified cinnamaldehyde (11.26%) and 2-hydroxyl cinnamaldehyde (6.7%) as the major components. A significant increase was observed in wound contraction ratio, fibroblast proliferation, collagen deposition, re-epithelialization and keratin biosynthesis in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05). The expression level of cyclin D1, IGF1, GLUT 1 and antioxidant capacity increased in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05).Conclusions: Topical administration of C. verum accelerated wound healing and can possibly be employed in treating the wounds of diabetic patients.

Identification of soybean peptide leginsulin variants in different cultivars and their insulin-like activities

We have recently reported that green soybean cultivar, echigomidori, and not the yellow cultivar, fukuyutaka, is a rich source of hormone-like peptide leginsulin consisting of 37 amino acids (Leg_1_37, PDB 1JU8A) and its C-terminal glycine deletant, Leg_1_36. Green soybean is mature, but the color of the seedcoat and cotyledon remains green. Therefore, in this study, we examined the leginsulin content in different varieties of 11 colored soybeans (including green, yellow, red, brown and black) and edamame (immature soybean). Profile analysis of soybean constituents by LC-MS showed that Leg_1 (36 + 37) detected as a prominent peak in 3 green and 1 yellow soybean cultivar was the strongest contributor in principal component analysis, indicating Leg_1 is the most characteristic feature for distinguishing soybean cultivars. However, smaller amounts of leginsulin-like peptides, defined as Leg_2 and Leg_3, were detected in other samples. The cDNA sequences and LC-MS/MS analyses revealed that Leg_2 was a homologue of Leg_1 with three amino acid substitutions derived from SNPs, while Leg_3 was a Leg_1/Leg_2 paralog. Expression levels of Leg_1 were markedly higher than Leg_2 and Leg_3. Additionally, in glucose uptake assay, purified TRX-His-tag fused recombinant Leg_1_37 prepared by bacterial expression showed stronger insulin-like activities than other variants including Leg_2, Leg_3, and their Gly deletants in myotube-like differentiated L6 and C2C12 cells. These results suggest that dietary consumption of soybean seed, especially including a higher amount of Leg_1_37, could be useful for lowering of blood glucose.

Chronic heat stress increases insulin-like growth factor-1(IGF-1) but does not affect IGF-binding proteins in growing pigs

The insulin-like activity of insulin-like growth factor-1 (IGF-1) is heavily blunted by IGF binding proteins (IGFBPs, including IGFBP-1 and IGFBP-3). The effects of heat stress (HS) on the IGF-1 and IGFBPs in growing pigs are still not clear. This study aimed to investigate the alterations of IGF-1 and IGFBPs under chronic HS in growing pigs. Twenty-seven growing large white barrows with similar body weight were collected from nine litters and were assigned into three treatments. The litter effect is balanced in all treatments. Treatments were: 1) thermal-neutral (TN) group (23 °C), 2) chronic HS group (33 °C), and 3) pair-fed in TN condition (PFTN). The experiment lasted for 21 days. Compared with TN controls, decreased FI, lower average body weight gain, higher rectal temperature and increased respiration rates were observed in HS pigs. On D7, increased plasma insulin concentration and insulin:glucose ratio were observed in HS pigs compared to TN controls. A overall elevation of plasma IGF-1:IGFBP-3 ratio was detected in HS pigs compared with PFTN and TN counterparts. Besides, hepatic IGF-1 gene expression of HS pigs was 50% higher than TN counterparts. PFTN pigs, however, had no differences in plasma IGF-1:IGFBP-3 ratio and hepatic IGF-1 gene expression, compared with TN pigs. PFTN pigs increased plasma IGFBPs concentration and hepatic IGFBPs gene expression, compared with TN controls. However, no differences in plasma IGFBPs concentration and hepatic IGFBPs gene expression were observed between TN and HS group. Liver IRS-1 gene and protein expressions of HS pigs tended to be increased compared with TN controls, while PFTN pigs still kept liver IRS-1 gene and protein expressions in normal level. High temperature (33 °C), independent of feed intake reduction, increased IGF-1 but did not affect IGFBPs levels in growing pigs.