RIN-5F Cells Research Articles

Multifaceted therapeutic approach via thiazolidinedione-infused magnolol in chitosan nanoparticles targeting hyperlipidemia and oxidative stress in gestational diabetes mellitus in experimental mice.

Recent advancements in nanotechnology have sparked interest in the synthesis of chitosan nanoparticles and their potential applications in medicine. This study investigates the synthesis of chitosan nanoparticles infused with thiazolidinedione and magnolol (TZ/ML-ChNPs) and their therapeutic effects on gestational diabetes mellitus (GDM) in experimental mice. Using streptozotocin-induced diabetic pregnant mice as a model, the study examines the anti-diabetic effects of TZ/ML-ChNPs in vitro and explores possible mechanisms of action. Results show a notable decrease in α-amylase and α-glucosidase activities in TZ/ML-ChNPs-treated samples. Cytocompatibility and flow cytometry analysis in streptozotocin-induced diabetic pregnant mice conducted on RIN-5F cell line demonstrate the safety profile of TZ/ML-ChNPs. The primary objective of this research is to assess whether TZ/ML-ChNPs can mitigate hyperlipidemia and oxidative stress in diabetic pregnant mice. Chitosan nanoparticles with thiazolidinedione and magnolol have therapeutic effects that may be used in clinical and pharmaceutical applications.

Effect of bovine beta-casomorphins on rat pancreatic beta cells (RIN-5F) under glucotoxic stress

Beta-casomorphins (BCMs) are the bio-active peptides having opioid properties which are formed by the proteolytic digestion of β-caseins in milk. BCM-7 forms when A1 milk is digested in the small intestine due to a histidine at the 67th position in β-casein, unlike A2 milk, which has proline at this position and produces BCM-9. BCM-7 has further degraded into BCM-5 by the dipeptidyl peptidase-IV (DPP-IV) enzyme in the intestine. The opioid-like activity of BCM-7 is responsible for eliciting signaling pathways which enable a wide range of physiological effects. The aim of our study was to find out the differential role of BCMs (BCM-7, BCM-9 and BCM-5) on pancreatic β-cell proliferation, insulin secretion, and opioid peptide binding receptors from β-cells (RIN-5F cell line) in normal (5.5 mM) and high glucose (27.5 mM) concentrations. Our results showed that BCM-7/9/5 did not affect β-cell viability, proliferation, and insulin secretion at normal glucose level. However, at higher glucose concentration, BCMs significantly protected β-cells from glucotoxicity but did not affect the insulin secretion. Interestingly, in the presence of Mu-opioid peptide receptor antagonist CTOP, BCMs did not protect β-cells from glucotoxicity. The results suggest that BCMs protect β-cells from glucotoxicity via non-opioid mediated pathways because BCMs did not modulate the gene expression of the mu, kappa and delta opioid peptide receptors.

X Ray-Induced Insulinoma Cell Line Rin-5F Has a Novel Mutation Site, C.A1459G (P.T487A), in Death Domain Associated Protein (DAXX) Gene

A popular toxicological and pharmacological research cell line is the insulin-secreting pancreatic cell line Rin-5F. The cell line originates from insulinomas induced by X-ray exposure. The author of this report looked at the mutation status of the DAXX gene in the Rin-5F cell line clone.<em> </em>The complete DNA and RNA were extracted from the cultivated cells as well. Double-stranded cDNA was then synthesized using the RNA template. Sequencing was done using a 3730xl DNA Analyzer.<em> </em>In the present study, c.A1459G (p.T487A) in Exon 5 in the DAXX gene was detected in Rin-5F cell lines, one of the X-ray-induced insulinomas. An NCBI homology search reveals that the 487 amino acid site in rats is the 497 amino acid of humans, based on the genomic cDNA homology between rats and humans. In humans, the COSMIC database suggests that mutations involving 497 amino acids have not been detected in all human cancers. However, the mutation of 496 amino acids was detected in human stomach and colon cancers. This is the first account of the DAXX gene's state in a cell line created by exposure to X-rays. This may point to the need for additional data and research on unique gene alterations involved in the development of X-ray-induced insulinoma tumors.

Cytotoxic Impact of Naringenin-Loaded Solid Lipid Nanoparticles on RIN5F Pancreatic β Cells via Autophagy Blockage.

Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability. This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact. In vitro experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F. Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar. These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5F cell growth.

In vitro and functional investigation reveals the curative effect of thymoquinone from black cumin-loaded chitosan nanoparticles on streptozotocin induced paediatric diabetes

Diabetic ketoacidosis (DKA) is regarded to be a communal complication of both type 1 and type 2 diabetes mellitus in children and adolescents. Successful therapy of DKA in children requires prompt diagnosis, strict monitoring of medical indicators, and prompt action. Thymoquinone (Tq) from black cumin loaded chitosan nanoparticles (ChNPs) intend to assess an effective agent to overcome this problem. XRD, FTIR, SEM, and TEM were used in the physicochemical analysis. Enzymatic activity of α-amylase and α-glucosidase was used in in vitro tests of anti-diabetic efficacy. Protecting insulin against enzyme breakdown is a crucial part of the insulin delivery mechanism. In the STZ-induced diabetes RIN-5F cell line, the anti-apoptotic capability of Tq-ChNPs was demonstrated through the NF-κB mediated apoptotic pathway. The combination of thymoquinone and chitosan NPs demonstrated that a wide variety of incredibly effective substances to elevate their curative effects, thus contributing to the growth of clinical and pharmaceutical fields.

Exploring the potential of Lindernia ciliata: isolation, characterization, and pharmacological evaluation of its anti-diabetic properties

We isolated two phytoconstituents using bioassay guided isolation for anti-diabetic property from the hydroalcoholic extract of Lindernia ciliata (Colsm.) Pennell (Family: Linderniaceae). We assessed the anti-diabetic potential using various assays, including the glucose absorption assay, glucose uptake in isolated rat abdominal muscle assay, insulin secretion by RIN-5F cells assay, α-amylase inhibition activity, and DPP-4 inhibition assay. The results from our study indicated that the ethanol and water fractions obtained from the hydroalcoholic extract significantly improved glucose uptake, demonstrating promising anti-diabetic properties. Further investigation led to the isolation of two distinct compounds, LCF-1 (IUPAC name: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one) (LCF-1) and LCF-2 (IUPAC name: 3S,10R,13R,17R)-17-[(2R,5R)-5-ethyl-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol). Consequently, our findings suggest that LCF-1 and LCF-2 are two phytoconstituent derived from the hydroalcoholic extract of L. ciliata, could serve as a potential source of anti-diabetic agents. This highlights its suitability for further development in the creation of herbal pharmaceuticals for diabetes treatment.

In silico design and identification of new peptides for mitigating hIAPP aggregation in type 2 diabetes

The aberrant misfolding and self-aggregation of human islet amyloid polypeptide (hIAPP or amylin) into cytotoxic aggregates are implicated in the pathogenesis of type 2 diabetes (T2D). Among various inhibitors, short peptides derived from the amyloidogenic regions of hIAPP have been employed as hIAPP aggregation inhibitors due to their low immunogenicity, biocompatibility, and high chemical diversity. Recently, hIAPP fragment HSSNN18-22 was identified as an amyloidogenic sequence and displayed higher antiproliferative activity to RIN-5F cells. Various hIAPP aggregation inhibitors have been designed by chemical modifications of the highly amyloidogenic sequence (NFGAIL) of hIAPP. In this work, a library of pentapeptides based on fragment HSSNN18-22 was designed and assessed for their efficacy in blocking hIAPP aggregation using an integrated computational screening approach. The binding free energy calculations by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method identified HSSQN and HSSNQ that bind to hIAPP monomer with a binding affinity of −21.25 ± 4.90 and −19.73 ± 3.10 kcal/mol, respectively, which is notably higher as compared to HSSNN (–11.90 ± 4.12 kcal/mol). The sampling of the non aggregation-prone helical conformation was notably increased from 23.5 ± 3.0 in the hIAPP monomer to 38.1 ± 3.6, and 33.8 ± 3.0% on the incorporation of HSSQN, and HSSNQ, respectively, which indicate reduced aggregation propensity of hIAPP monomer. The pentapeptides, HSSQN and HSSNQ, identified as hIAPP aggregation inhibitors in this work can be further conjugated with various metal chelating peptides to yield more efficacious and clinically relevant multifunctional modulators for targeting various pathological hallmarks of T2D.

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes.

Luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid commonly present in Mentha longifolia L. and Olea europaea L. leaves has been used as a flavoring agent with some biological activity. The present study is the first attempt to analyze the protective effect of lut-7-O-rutin on high-glucose-induced toxicity to RIN-5F cells in vitro. We found that lut-7-O-rutin improved insulin secretion in both normal and high-glucose conditions in a dose-dependent manner, without toxicity observed. In addition, 20 µmol of lut-7-O-rutin improves insulin sensitization and glucose uptake significantly (p ≤ 0.01) in L6 myotubes cultured in a high-glucose medium. Lut-7-O-rutin has shown a significant (p ≤ 0.05) effect on glucose uptake in L6 myotubes compared to the reference drug, rosiglitazone (20 µmol). Gene expression analysis confirmed significantly lowered CYP1A, TNF-α, and NF-κb expressions in RIN-5F cells, and increased mitochondrial thermogenesis-related LPL, Ucp-1 and PPARγC1A mRNA expressions in L6 myotubes after 24 h of lut-7-O-rutin treatment. The levels of signaling proteins associated with intracellular glucose uptakes, such as cAMP, ChREBP-1, and AMPK, were significantly increased in L6 myotubes. In addition, the levels of the conversion rate of glucose to lactate and fatty acids were raised in insulin-stimulated conditions; the rate of glycerol conversion was found to be higher at the basal level in L6 myotubes. In conclusion, lut-7-O-rutin protects RIN-5F cells from high-glucose-induced toxicity, stimulates insulin secretion, and promotes glucose absorption and homeostasis via molecular mechanisms.

Amelioration of Streptozotocin Induced Cytotoxicity by <i>Mimosa pudica</i> Root Extract - A Proteomic Based In-Vitro Study

The in-vitrocytotoxicity was studied in a pancreatic cell line (RIN5F) using streptozotocin-induced cellular damage. The Cytotoxic dose of aqueous and hydro-alcoholic extracts of Mimosa pudica root powder before and after streptozotocin treatment was studied and protein expression was explored. Both the extracts were subjected to metabolite analysis by LCMS. Mimosa pudica root powder extracts prevented Streptozotocin-induced cellular damage. Proteomics studies indicated both aqueous and hydro-alcoholic extracts of Mimosa pudica regulate proteins related to insulin secretion, glucose uptake, and insulin resistance with marked changes in proteins involved in insulin secretion. The study first time reports cytotoxicity of Mimosa pudica in RIN5F cells and explores protein expression after Mimosa pudica treatment. It was also observed that the abundance of Mimosine is more in Hydro-alcoholic extracts as compared to aqueous extracts.

Molecular targeting of prodigiosin against anti-inflammatory genes cyclooxygenase-1 and -2

The prodigiosin produced by the bacteria Serratia marcescens (SM) has been isolated and optimized with the streak plate method from different natural sources, such as human urine (SM1), soil (SM2), vegetable matter (Cucurbita maxima, SM3) and water (SM4). The isolated prodigiosin was confirmed as SM by its morphological characteristics, genomic size (1.5 kb), identification, and protein purification (4 kDa) using SDS-PAGE. Further, the total cell protein was confirmed and purified through thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The prodigiosin exhibited good microbial activity against selected Gram-positive bacteria and fungi. The binding efficiency of prodigiosin against cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) genes was assessed using an in silico molecular docking method that suggested higher binding efficiency for COX-2 than COX-1. Further, prodigiosin was nontoxic to rat islet (RIN-5F) cells in an assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylteterazolium bromide) in vitro, and its morphological characteristics of cell shape, clumping, chromatin, and nuclear morphology were normal when viewed under bright light microscopy. Finally, prodigiosin was tested for anti-inflammatory properties against lipopolysaccharide-induced RIN-5F cells. The tests revealed that prodigiosin protected against elution of inflammatory markers like NO, interleukin-6 (IL6), and IL8 in a dose-dependent manner.

Study of in vitro activity on glucose uptake of 3T3L1 cells, RIN5f cells, and glycemic index stimulation inhibitory effect of Abutilon indicum (L.) extract

Study of in vitro activity on glucose uptake of 3T3L1 cells, RIN5f cells, and glycemic index stimulation inhibitory effect of Abutilon indicum (L.) extract

Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions.

The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose (HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4 expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the above-stated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to attenuate cell death after the cytokines' treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.

Gymnemic Acid Ameliorates Pancreatic β-Cell Dysfunction by Modulating Pdx1 Expression: A Possible Strategy for β-Cell Regeneration.

Endogenous pancreatic β-cell regeneration is a promising therapeutic approach for enhancing β-cell function and neogenesis in diabetes. Various findings have reported that regeneration might occur via stimulating β-cell proliferation, neogenesis, or conversion from other pancreatic cells to β-like cells. Although the current scenario illustrates numerous therapeutic strategies and approaches that concern endogenous β-cell regeneration, all of them have not been successful to a greater extent because of cost effectiveness, availability of suitable donors and rejection in case of transplantation, or lack of scientific evidence for many phytochemicals derived from plants that have been employed in traditional medicine. Therefore, the present study aims to investigate the effect of gymnemic acid (GA) on β-cell regeneration in streptozotocin-induced type 1 diabetic rats and high glucose exposed RIN5-F cells. The study involves histopathological and immunohistochemical analysis to examine the islet's architecture. Quantitative polymerase chain reaction (qPCR) and/or immunoblot were employed to quantify the β-cell regeneration markers and cell cycle proliferative markers. The immunoexpression of E-cadherin, β-catenin, and phosphoinositide 3-kinases/protein kinase B were significantly increased in GA-treated diabetic rats. On the other hand, treatment with GA upregulated the pancreatic regenerative transcription factor viz. pancreatic duodenal homeobox 1, Neurogenin 3, MafA, NeuroD1, and β-cells proliferative markers such as CDK4, and Cyclin D1, with a simultaneous downregulation of the forkhead box O, glycogen synthase kinase-3, and p21cip1 in diabetic treated rats. Adding to this, we noticed increased nuclear localization of Pdx1 in GA treated high glucose exposed RIN5-F cells. Our results suggested that GA acts as a potential therapeutic candidate for endogenous β-cell regeneration in treating type 1 diabetes.

Bio nanocomposites of graphene oxide with carboxymethyl guargum: fabrication and characterization and application for type 1 diabetes

Islet cells transplantation has limitations like low survivability, which can be overcome by using extracellular matrix mimicking three-dimensional (3D) scaffolds, which supports the growth and proliferation of seeded cells. This study was aimed to investigate the role of novel 3D carboxymethyl guargum (CMGG) nanocomposite with reduced graphene oxide (rGO) for proliferation of pancreatic islet cells (RIN-5F) and rate of insulin secretion of RIN-5F cells. Scanning electron microscope and Fourier transform infrared results have demonstrated good porosity and the chemical interactions between CMGG and rGO. Mechanical testing and thermogravimetric analysis of nanofibers have shown good tensile strength and thermal stability with rGO in the nanocomposite. These scaffolds demonstrated in vitro biocompatibility with acceptable ranges of biodegradability and hemocompatibility. The in vitro cell proliferation and viability of RIN-5F cells on 3D CMGG nanofibers have significantly increased compared to two-dimensional (2D) cell control. Moreover, the glucose dependent insulin secretion of RIN-5F cells on CMGG nanocomposite has significantly increased upto 4–5 folds than cells on 2D cell control. The biomaterials used in this 3D nanofiber scaffold have shown to be biodegradable and hemocompatible and can be a promising platform for the proliferation and secretion of insulin from beta cells and can be effectively used in transplantation type-1 diabetes.

In vitro anti-diabetic activity, bioactive constituents, and molecular modeling studies with sulfonylurea receptor1 for insulin secretagogue activity of seed extract of Syzygium cumini (L.)

Introduction: Syzygium cumini (L.) has been known to be used for diabetes treatment in traditional Indian and Chinese medicine. The present study focuses on the evaluation for glucose uptake and insulin release in vitro and characterization of phytoconstituents of the hydro-ethanolic extract of Syzygium cumini seed (SCE). Further, this report covers the molecular docking findings of the bioactive constituents on the sulfonylurea receptor 1 (SUR1). Methods: A glucose uptake assay of SCE was used to estimate the glucose uptake from the cell lysates and the cell culture supernatants using insulin as the reference standard. Insulin release activity of SCE from RIN-5F cells was estimated using enzyme-linked immunosorbent assay. The phytoconstituents were isolated by preparative HPLC and characterized by mass spectrometry, nuclear magnetic resonance (NMR) and infrared spectroscopy. The molecular docking of bioactive constituents was carried on repaglinide bound to the SUR1. Results: In the presence of SCE, the glucose uptake through L6 myoblast cells increased by 19.91% at 40 µg/mL in comparison with the vehicle control (P < 0.05). Moreover, SCE showed 2.8-fold enhancement of insulin release at 40 µg/mL as compared to the vehicle controls (P < 0.05). Gallic and ellagic acids were the key phytoconstituents isolated from SCE. Molecular docking studies revealed that both gallic acid and ellagic acid bind to the repaglinide binding pocket of SUR1. Conclusion: SCE increases the release of insulin and enhances glucose uptake in vitro, which may contribute to its in vivo anti-diabetic activity. The presence of ellagic acid and gallic acid in SCE may be the cause for enhanced insulin release observed with SCE following binding to SUR1.

Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent Mechanism.

The accumulation of lipid intermediates may interfere with energy metabolism pathways and regulate cellular energy supplies. As increased levels of long-chain acylcarnitines have been linked to insulin resistance, we investigated the effects of long-chain acylcarnitines on key components of the insulin signalling pathway. We discovered that palmitoylcarnitine induces dephosphorylation of the insulin receptor (InsR) through increased activity of protein tyrosine phosphatase 1B (PTP1B). Palmitoylcarnitine suppresses protein kinase B (Akt) phosphorylation at Ser473, and this effect is not alleviated by the inhibition of PTP1B by the insulin sensitizer bis-(maltolato)-oxovanadium (IV). This result indicates that palmitoylcarnitine affects Akt activity independently of the InsR phosphorylation level. Inhibition of protein kinase C and protein phosphatase 2A does not affect the palmitoylcarnitine-mediated inhibition of Akt Ser473 phosphorylation. Additionally, palmitoylcarnitine markedly stimulates insulin release by suppressing Akt Ser473 phosphorylation in insulin-secreting RIN5F cells. In conclusion, long-chain acylcarnitines activate PTP1B and decrease InsR Tyr1151 phosphorylation and Akt Ser473 phosphorylation, thus limiting the cellular response to insulin stimulation.

THE INSULINOTROPIC EFFECT OF THIAZOLIDINEDIONE DERIVATIVES IN TYPE II DIABETIC MODEL, RIN-5F CELLS, AND ITS ACTION ON CULTURED HUMAN LUNG FIBROBLAST SHOWS OXYGEN FREE-RADICAL SCAVENGING ACTIVITY

Objective: Diabetes mellitus is a persistent disorder caused by deficiency in insulin production. Oxidative stress plays an important role in physiopathology of diabetes. The present research determined the antidiabetic and antioxidant effects of 5-naphthalidin thiazolidinediones derivatives.
 Methods: Both in vitro and in vivo experiments were carried out on diabetes induced male Swiss albino rats by single intramuscular injection of alloxan (0.15 mg/kg i.m) and IDDM-rats received 4b, 4c, or 4d (36 mg/kg, p.o). The derivatives were further subjected to insulin secretion by RIN-5F cells confirmed insulinotropic effect. In vitro antioxidant activity was evaluated using enzymatic activities on cell lines In addition, all the synthesized derivatives showed non-toxic effects against a diseased human lung fibroblast (COPD), HCC7231 (TACC CCL-96).
 Results: The results revealed that 4b, 4c, and 4d showed promising results by substantially lowering the blood glucose levels on 21st day of post-administration. Serum insulin levels substantially rose, suggesting that derivatives exert insulinotropic effects through different pathways. 4c showed oxygen free-radical scavenging activity.
 Conclusion: Our study proves that oral administration of 5-naphthalidin-TZD twice a day is a valuable treatment for type II diabetes. It seems to be a good drug moiety endowed significant oxygen free-radical scavenging activity.

Identification of sphingosine 1-phosphate level and MAPK/ERK signaling in pancreatic β cells.

Purpose Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F.Methods RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting.Results Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells.Conclusions We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.

In vitro and in vivo antidiabetic activity of Tamarix stricta Boiss.: Role of autophagy

Ethnopharmacological relevanceType 2 diabetes mellitus (DM) is a complicated metabolic disorder with no definite treatment. Different species of the genus Tamarix (tamarisk) are used by local people to treat DM. Tamarix stricta Boiss. is an endemic species to Iran with several traditional therapeutic uses in Persian Medicine. This study aimed to assess the antidiabetic activity of T. stricta. Materials and methodsHydroethanolic extract of the plant was prepared and analyzed by High-performance liquid chromatography (HPLC). The protective effect of the extract was evaluated in streptozotocin (STZ)-induced toxicity and markers of autophagy in pancreatic RIN-5F cells. The effect of intragastric 10 or 20 mg/kg of the extract was compared with negative control (water) or positive control (metformin) treatment during four weeks of administration in high-fat diet + STZ-induced DM in Balb/c mice. ResultsResults showed the presence of 8.436 mg of gallic acid in each gram of the extract. A significant cytoprotective effect was observed by T. stricta in STZ-induced toxicity in RIN-5F cells, partially due to the modulation of autophagy. Also, animals treated with the extract showed a significant improvement in glycemic and lipid profiles, liver function, and histopathologic features of pancreas and liver compared with the negative control. ConclusionT. stricta demonstrated beneficial effects in animal model of DM; though, further studies are recommended to confirm the clinical use of this plant in DM.

In Vitro Antidiabetic and Antioxidant Effects of Different Extracts of Catharanthus roseus and Its Indole Alkaloid, Vindoline.

The Catharanthus roseus plant has been used traditionally to treat diabetes mellitus. Scientific evidence supporting the antidiabetic effects of this plant’s active ingredient-vindoline has not been fully evaluated. In this study, extracts of C. roseus and vindoline were tested for antioxidant activities, alpha amylase and alpha glucosidase inhibitory activities and insulin secretory effects in pancreatic RIN-5F cell line cultured in the absence of glucose, at low and high glucose concentrations. The methanolic extract of the plant showed the highest antioxidant activities in addition to the high total polyphenolic content (p < 0.05). The HPLC results exhibited increased concentration of vindoline in the dichloromethane and the ethylacetate extracts. Vindoline showed noticeable antioxidant activity when compared to ascorbic acid at p < 0.05 and significantly improved the in vitro insulin secretion. The intracellular reactive oxygen species formation in glucotoxicity-induced cells was significantly reduced following treatment with vindoline, methanolic and the dichloromethane extracts when compared to the high glucose untreated control (p < 0.05). Plant extracts and vindoline showed weaker inhibitory effects on the activities of carbohydrate metabolizing enzymes when compared to acarbose, which inhibited the activities of the enzymes by 80%. The plant extracts also exhibited weak alpha amylase and alpha glucosidase inhibitory effects.