MLPH/RAB3A accelerates the differentiation of pancreatic stem cells to islet β-cells to control blood glucose in diabetic rats
ABSTRACT Background This study aimed to determine the potential mechanism by which pancreatic stem cell-derived beta cells (PSCs-β) assist in the body's glucose-lowering capacity in type 1 diabetes (T1D) rats. Methods We screened the transcriptomic changes in the pancreatic islets of T1D mice to extract key genes from the GSE169275 dataset. Cell proliferation, cell cycle distribution, apoptosis, PSC-β differentiation ability, and insulin production levels were analyzed after MLPH overexpression/knockdown in PSCs. PSC-β-overexpressing MLPH were transplanted into T1D rats, and the changes in fasting blood glucose level, glucose tolerance and insulin, glucagon and C-peptide contents were examined. After the target genes of MLPH were analysed using the database, immunoprecipitation was introduced for validation. Whether RAB3A is involved in the regulatory effects of MLPH on the proliferation and differentiation of PSCs was further verified. Results MLPH overexpression further enhanced the proliferation of PSCs, inhibited apoptosis and accelerated the differentiation of PSCs to PSC-β cells and insulin secretion. After the transplantation of MLPH-overexpressing PSC-β cells, the pancreatic islet tissue damage was restored, the insulin expression was substantially elevated and the glucagon content decreased. RAB3A knockdown counteracted the effects of MLPH on the proliferation, differentiation and insulin secretion of PSCs. Conclusion MLPH overexpression is favourable for the differentiation of PSCs to insulin β-cells. Transplantation of MLPH-overexpressing PSC-β cells restored the ability of T1D rats to manage a glycemic load by promoting RAB3A expression.
- Research Article
11
- 10.1007/s12192-016-0679-3
- Feb 22, 2016
- Cell Stress and Chaperones
Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats.
- Research Article
13
- 10.1089/jmf.2018.4237
- Jan 1, 2019
- Journal of Medicinal Food
This study aimed to examine the antidiabetic effects of various concentrations of adlay bran oil (ABO) in high fat diet and streptozotocin-induced diabetic rats. Dietary supplementation with 10% ABO for 4 weeks effectively decreased the blood triacylglycerol, glucose, and total cholesterol levels in diabetic rats, although body weight remained the same. The mRNA and protein expressions of hepatic glucose transporter 2 (GLUT-2) and phosphoenolpyruvate carboxykinase (PEPCK) were increased and that of glucokinase (GCK) were decreased in diabetic rats. However, 10% ABO treatment reduced the mRNA and protein expressions of GLUT-2 and PEPCK and elevated the expression of hepatic GCK in diabetic rats. Thus, ABO enhanced hepatic glucose metabolism to decrease blood glucose in diabetic rats. In addition, 10% ABO supplementation increased the expression of phosphorylated protein kinase B (Akt) relative to the total Akt levels in the muscles of diabetic rats, indicating enhanced insulin sensitivity. The results indicate that ABO displays a potential for improving hyperlipidemia and hyperglycemia in diabetes by enhancing insulin sensitivity and hepatic glucose metabolism.
- Research Article
17
- 10.22038/ajp.2015.3980
- Jan 1, 2015
- Avicenna Journal of Phytomedicine
Objectives: Turnip leaf has been used in folk medicine of Iran for the treatment of diabetes. However,so far no scientific study has been done to support its use in traditional medicine. The present study was carried out to evaluate the possible hypoglycemic efficacy of aqueous extract of turnip leaf (AETL) in diabetic rats.Materials and Methods:Alloxan-induced diabetic rats were orally treated with AETL at doses of 200 and 400 mg/kg body weight (bw) per day for 28 days. In order to evaluate the anti-diabetic activity, fasting blood glucose concentrations were determined on the 1st, 14th and 29th days. Moreover,at the end of the study, plasma concentrations of total cholesterol, triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), aspartate amino transfarase (AST), and alanine amino transferase (ALT) were measured by the use of standard kits and auto-analyzer.Results:Both doses of AETL significantly decreased (p<0.001) blood glucose and ALT levels in diabetic rats after 28 days of administration. AETL at both doses decreased (p<0.05) plasma total cholesterol and LDL-c in diabetic rats, but they significantly decreased (p<0.05) HDL-c and increased triglycerideand AST levels in a-dose dependent manner.Conclusion: The results showed that AETL has a dose- dependent decrease in the blood glucose in diabetic rats. However,we should not be unaware of adverse effects of AETL on lipid profiles and liver enzymes activity, especially decrease of HDL and increase of TG and AST.
- Research Article
98
- 10.1016/j.pathophys.2010.08.003
- Sep 24, 2010
- Pathophysiology
Antihyperglycemic and hypolipidemic activities of Setaria italica seeds in STZ diabetic rats
- Research Article
- 10.53350/pjmhs221651135
- May 30, 2022
- Pakistan Journal of Medical and Health Sciences
Objective: Probiotics were compared to Sitagliptin in this research in order to see whether they might lower blood glucose levels in diabetic rats more effectively. Study Design: Quasi experimental study Place and Duration: Fatima Jinnah Medical University Lahore. Jan, 2021 to June, 2021 Methods: There were 80 male rats were presented in this study. We used Streptozotocin to inflict diabetes in rats, and after one week, the results were validated by measuring Fasting Blood Glucose (FBG) (>7 mmol/L was termed diabetic). Rats were divided in four groups. Group I had 20 diabetic control rats, group II had 20 rats and received probiotics (250 mg/Kg), group III received sitagliptin (10 mg/Kg) among 20 rats and group IV received combination of probiotics and sitagliptin. Blood glucose was measured at baseline and after 6-weeks. Results among all groups were compared. SPSS 24.0 was used to analyzed all data. Results: We observed that rats given probiotics in group-II saw a substantial drop in their fasting blood glucose levels, with an effectiveness that was on par with that of rats given sitagliptin in group-III (p 0.05). Sitagliptin and probiotics had a synergistic impact in group IV that was stronger (p<0.05) than either of their individual effects in groups II and III. Conclusion: We concluded that Sitagliptin plus Probiotics lowers diabetic rats' blood glucose more than individual medicines. Probiotics reduce fasting blood glucose in diabetic rats like Sitagliptin. Diabetes treatment can include probiotics. Keywords: Diabetes mellitus, Fasting blood glucose, Sitagliptin, Probiotics, Rats
- Research Article
70
- 10.1016/j.biochi.2014.08.006
- Aug 20, 2014
- Biochimie
Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats.
- Research Article
- 10.54615/2231-7805.10001117
- Jan 1, 2024
- ASEAN Journal of Psychiatry
Diabetes mellitus is a silent killer that claims about 2 million lives annually. Endoplasmic-reticulum (ER) stress has been linked to type-2 diabetes. This study evaluated the effect of Bambusa vulgaris leaf ethanolic extract (B.V.E.E.) on ER-stress induced by Streptozotocin (STZ) in rats. Rats were divided into six groups and induced with the diabetes using streptozotocin (65 mg/kg) except the control group. Bambusa vulgaris (100, 200 and 400 mg/kg) were administered to the induced rats for twenty-one (21) days. The rats were sacrificed and blood collected for haematology while the liver was harvested for biochemical analysis. The expression of [(activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), tribbles 3 (TRB3), transcription factor C/EBP homologous protein (CHOP), IRE1, interleukin 6 (IL-6), interleukin 1? (IL-1?) and tumor necrosis factor alpha (TNF-?)] genes was done using reverse transcriptase polymerase chain reaction (RT-PCR). Result showed that B.V.E.E. reduced fasting blood glucose in diabetic rats and lowered the activity of AST, ALT and ALP when compared to diabetic un-treated rats. Administration of B.V.E.E. promoted mitochondria biogenesis, reversed inflammation and glucose insensitivity in the pancreas of diabetic ER stress rats via modulation of GADPH, TRB3, CHOP, TNF-?, IL-1? and IL-6 mRNA expressions. B.V.E.E. administration inhibited diabetic ER stress-induced cell apoptosis by depleting the mRNA expression of ER stress sensors (IRE1, ATF4, ATF6 and PERK). Furthermore, B.V.E.E. ameliorated the increased lipid profiles in diabetic rats and restored renal function as shown by lowering the activity of AST, ALT and ALP. as well as restore distorted full blood in diabetic rats. Finally, in silico studies showed that taxiphyllin had the highest binding affinity of all the compounds present in the B. vulgaris leaf and may be the potent compound responsible for mitigation ER stress in the liver. Hence, B.V.E.E. may be deployed as medicinal plant in diabetic ER-stress management and safe for consumption, while taxiphyllin was implicated for the anti-diabetic and anti-inflammatory properties. Keywords Diabetes; Medicinal plant; Therapy; Oxidative stress; Bamboo
- Research Article
64
- 10.1007/s10534-009-9241-4
- Apr 29, 2009
- BioMetals
Vanadium(III, IV, V)-chlorodipicolinate (dipic-Cl) complexes, including H[VIII(dipic-Cl)2] · 5H2O (V3dipic-Cl), VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[VVO2(dipic-Cl)] (V5dipic-Cl), were prepared with the indicated oxidation states. Our aim was to evaluate the anti-diabetic effects of V3dipic-Cl, V4dipic-Cl and V5dipic-Cl in streptozotocin-induced diabetic rats. Vanadium complexes were orally administered to diabetic rats at concentrations of 0.1-0.3 mg/ml in the drinking water. We found that vanadium-chlorodipicolinate (V-dipic-Cl) complexes at the concentration of 0.1 mg/ml did not exhibit blood glucose-lowering effects when administered to diabetic rats for 20 days. However, the levels of fasting blood glucose in diabetic rats were decreased after treatment with 0.3 mg/ml of V4dipic-Cl and V5dipic-Cl complexes for the following 20 days. Although administration of both V4dipic-Cl and V5dipic-Cl significantly lowered diabetic hyperglycemia, the vanadium intake from administration of V4dipic-Cl is nearly 1.5-fold greater compared to that of V5dipic-Cl. Treatment with the H2dipic-Cl ligand and all three V-dipic-Cl complexes significantly lowered serum cholesterol, while administration of the V5dipic-Cl complex lowered serum cholesterol significantly more than administration of the ligand alone. Treatment with ligand alone did not have an effect on serum triglyceride, while administration of the V4dipic-Cl and V5dipic-Cl significantly lowered the elevated serum triglyceride associated with diabetes. Oral administration of the ligand and all V-dipic-Cl complexes did significantly lower diabetes elevated serum alkaline phosphatase. Treatment with H2dipic-Cl ligand and V4dipic-Cl and V5dipicCl significantly lowered diabetes elevated aspartate amino transferase. These results indicate that the health of the treated animals did not seem to be further compromised compared to that of diabetic animals. In addition, oral administration of H2dipic-Cl, V3dipic-Cl, V4dipic-Cl and V5dipic-Cl did not alter diabetic serum creatinine and blood urea nitrogen levels, suggesting no significant side effects of vanadium treatment on renal functions at the dose of 0.3 mg/ml in diabetic rats. The results presented here suggest that the anti-diabetic effects of treatment with V-dipic-Cl complexes were likely associated in part with the oxidation state of vanadium.
- Research Article
- 10.3760/cma.j.issn.1673-4181.2010.06.001
- Dec 28, 2010
- International Journal of Biomedical Engineering
Objective To study the effect of diabetes on spatial memory ability and spatial associative memory ability in rats. Methods 70 SD rats( 180±20 g) were randomly divided into 3 groups: control group,type1 diabetes group and type2 diabetes group. Type1 and type2 diabetic rat models were set up by streptozocin (STZ) intraperitoneal injection and high fat forage raise. The blood glucose was determined. After rat diabetic model established 1 month and 3 months, respectively, the Morris water maze experiments were implemented,including 4 days' place swimming and 1 day's space exploration. Results After 1 month, diabetic rats' spatial memory ability and spatial associative memory ability were not affected. After 3 months, in place swimming test,the escape latency of two diabetic rat groups was obviously longer than that of the control group (P<0.05). From the second day of the experiment, escape latency of the control descended sharply, while that of the diabetic group descended slowly. There was no difference between type 1 and type2 diabetic groups in escape latency (P>0.05). After 3 months, in the space exploration test, when rats were put into the maze from I quadrant which already trained, swimming time in the platform quadrant was shorter, the other parameter scores were lower of the two diabetic model groups, contrast to the control group (P<0.05). The parameter scores of type2 diabetic group were lower slightly than type1 diabetic group. When rats were put into the maze from IV quadrant for which never trained, the parameter scores of two diabetic groups were lower than that of the control group (P<0.05) and the total score of type 1 group was lower than that of type2 group. Conclusion The spatial memory ability and spatial associative memory ability of type 1 and type2 diabetic rats descended. In the experiment, the spatial memory ability of type2 diabetic rats was more significantly affected than that of type1 diabetic rats. By contrast,type 1 diabetic rats' spatial associative memory ability descended greatly than that of type2 diabetic rats. Key words: Type1 and type2 diabetes; Rats; Morris water maze; Spatial memory ability; Spatial associative memory ability
- Research Article
- 10.5958/2319-5886.2015.00026.0
- Jan 1, 2015
- International Journal of Medical Research & Health Sciences
Anti-fungal and antimicrobials are frequently co-prescribed either to manage or treat either the secondary complications or other diseases. Among antifungal drugs Fluconazole, Itraconazole & Voriconazole are most commonly used. The present study was undertaken to further confirm the effect of Voriconazole as well as other antifungal drugs on blood Glucose level. Aim & Objectives: 1. To Study the effect of Fluconazole, Itraconazole & Voriaconazole in Normoglycemic & Diabetic Rats on Blood Glucose. 2. To compare the effects between all drugs. Material & Methodology: Grouping: Animals divided into 8 groups in each group 6 animals. Group 1- 4: Normoglycemic rats, Group 5-8 Diabetic rats (alloxan induced) Group 1,5: received vehicle (Normal saline) Group 2,6: received Fluconazole (18mg/kg BW), Group 3,7 received Itraconazole (18mg/kg BW) Group 4,8 received Voriconazole (18mg/kg BW). The glucose levels were estimated by Glucometer method (Accu-check active) at the interval of 0, ½ hr, 1hrs, 2hrs & 4hrs after drug administration. Results: Effect on blood glucose in Normoglycemic Rats: Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value= 0.0102) of administration & persisted up to 2 hrs (‘p’ value=0.0001). However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in normoglycemic rats with Fluconazole & Itraconazole. Effect on blood glucose in Diabetic Rats: (Table 2): Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value=0.013) of administration & persisted up to 2 hrs (‘p’ value=0.001) in acute studies. However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in diabetic rats with Fluconazole & Itraconazole treated. Conclusion: Itraconazole, Fluconazole can be safely used in diabetic with fungal infections. Voriconazole should be avoided in diabetics to minimise the further hypoglycaemia.
- Research Article
2
- 10.1016/j.pathophys.2010.10.001
- Nov 3, 2010
- Pathophysiology
Heart rhythm disturbances in the neonatal alloxan-induced diabetic rat
- Research Article
36
- 10.1007/s11010-014-2107-2
- Jun 1, 2014
- Molecular and Cellular Biochemistry
Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150mg/kg body weight/day orally). After 30days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), β-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.
- Research Article
45
- 10.1016/j.biopha.2019.108897
- May 15, 2019
- Biomedicine & Pharmacotherapy
Diabetes-induced male sexual dysfunction is associated with endothelial dysfunction. Inhibition of soluble epoxide hydrolase (sEH) is known to improve endothelial function in diabetes. Therefore, we hypothesized that sEH inhibitor (sEHI), [trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid] / t-TUCB can restore the male sexual function in diabetic rat. After one week of administration of diabetogenic agent STZ (52 mg/kg i.p) injection, diabetic rats were treated with t-TUCB (0.1 and 0.3 mg/kg, p.o) or vehicle for 8 weeks. The sexual behaviour parameters of the animals were evaluated at the end of dosing period. The levels of testosterone and glucose in serum, and sperm were quantified. Effect of treatment on weight of reproductive organs and histopathology of penile tissue was evaluated. Diabetes had a negative effect on male sexual function, weight of sexual organs and production of sperm with a parallel decrease in the level of testosterone. The sEHI, t-TUCB, significantly preserved the sexual function and minimized an increase in the level of blood glucose in diabetic rats. It also prevented a decrease in the level of testosterone and sperm in diabetic rats, in comparison to diabetic control rats. Further, diabetes induced distortion of corpus cavernosum was attenuated by t-TUCB. Based on our findings, sEHI may delay the development of sexual dysfunction in diabetes.
- Research Article
10
- 10.1002/jbt.23463
- Aug 11, 2023
- Journal of Biochemical and Molecular Toxicology
Eupafolin is a phyto compound of flavone that exerts anti-inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide-streptozotocin (STZ)-induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA-IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)-2, GLUT4, PPARγ, and phosphatidylinositol 3-kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA-IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS-2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.
- Research Article
5
- 10.4268/cjcmm20152127
- Nov 1, 2015
- China Journal of Chinese Materia Medica
This article focused on a comparative analysis on the pharmacokinetic and pharmacodynamic characteristics of berberine (BER) and jateorhizine(JAT) in Coptidis Rhizoma powder (HL-P) and their monomeric compounds (BER + JAT, BJ) in type 2 diabetic (T2D) rats to explore the beneficial. effect of HL-P in the treatment of T2D. The T2D rats were treated with HL-P, BER, JAT and BJ, respectively for 63 d. The pharmacokinetic parameters, dynamic changes in blood glucose level and blood lipid values were measured. The results showed that, compared with other corresponding group, t(max), T(½ka) of BER and JAT in HL-P group were reduced, while C(max), AUC(inf), AUC(last), V(L)/F were significantly increased; compared with model group, blood glucose levels were decreased significantly in HL-P group since the 18th day, while those in BER or BJ group were reduced since the 36th day, however, blood glucose levels showed no obvious changes in JAT group; compared with model group, FFA values in all treatment group were decreased significantly. Moreover, TG, HDL and LDL value in HL-P group, LDL value in BER group and HDL value in BJ group were improved significantly. The above results showed that Coptidis Rhizoma powder showed excellent pharmacokinetic characteristics and excellent activity of lowering blood glucose and lipid. It provided a scientific basis for oral application of Coptidis Rhizoma powder in the treatment of T2D.