scholarly journals Impact of PCSK9 Immunization on Glycemic Indices in Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Amir Abbas Momtazi-Borojeni ◽  
Mahmoud Reza Jaafari ◽  
Elham Abdollahi ◽  
Maciej Banach ◽  
Amirhossein Sahebkar

Background and Aim. The impact of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on glycemic indices in diabetes mellitus remains far from clear. We explored the effects of PCSK9 inhibition on glycemic indices in the diabetes rat model. Methods. To prepare the anti-PCSK9 vaccine, a peptide construct called Immunogenic Fused PCSK9-Tetanus (IFPT) was linked to the surface of nanoliposome carriers. Healthy rats received four subcutaneous injections of the vaccine at biweekly intervals. Two weeks after the last vaccination, anti-PCSK9 antibody titers, PCSK9 targeting, and inhibition of PCSK9–low-density lipoprotein receptor (LDLR) interaction were evaluated. After verification of antibody generation, the immunized rats were intraperitoneally treated with a single dose (45 mg/kg) of streptozotocin (STZ) to induce diabetes mellitus. The levels of fasting blood glucose (FBG) were measured, and the oral glucose tolerance test (OGTT) as well as the insulin tolerance test (ITT) were carried out to assess glycemic status. At the end of the study, the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol concentrations were assayed. Histopathology examination of the liver and pancreas was also performed using the hematoxylin-eosin staining method. Results. The prepared nanoliposomal vaccine could strongly induce anti-PCSK9 antibodies in the vaccinated rats. Within one week following the STZ injection, the FBG level was lower in the vaccinated group vs. diabetic control group (49% ( − 171.7 ± 35   mg / dL , p < 0.001 )). In the OGTT, the injected rats showed improved glucose tolerance as reflected by the reduction of blood glucose levels over 180 min, compared with the diabetic controls. Moreover, the ITT demonstrated that, after the insulin injection, blood glucose concentration declined by 49.3% in the vaccinated group vs. diabetic control group. Expectedly, the vaccinated rats exhibited lower (-26.65%, p = 0.03 ) plasma LDL-C levels compared with the diabetic controls. Histopathology examination of pancreas tissue demonstrated that the pancreatic islets of the vaccinated rats had a slight decline in the population of β-cells and few α-cells. Normal liver histology was also observed in the vaccinated rats. Conclusion. PCSK9 inhibition through the liposomal IFPT vaccine can improve the glucose and insulin tolerance impairments as well as the lipid profile in diabetes.

2012 ◽  
Vol 5 (1) ◽  
pp. 161-170 ◽  
Author(s):  
R. Sharmin ◽  
M. R. I. Khan ◽  
Most. A. Akhtar ◽  
A. Alim ◽  
M. A. Islam ◽  
...  

Ethanolic extracts of some fruits of Cucurbitaceae family such as Cucumis sativus (cucumber), Lagenaria siceraria (white pumpkin), Luffa acutangula (ridge gourd), Benincasa hispida (ash gourd), Citrullus lanatus (sweet melon) and Cucarbita maxima (pumpkin) have been studied for their hypoglycemic effects on alloxan induced diabetic rats (AIDRs). Screening results suggested that among the tested fruits the hypoglycemic potency follows: cucumber > white pumpkin > ridge gourd. These three fruit-extracts were further investigated for their hypoglycemic, hypolipidemic and glycogenesis effects. Cucumber, white pumpkin and ridge gourd extracts reduced blood glucose level by 67, 65 and 51%, respectively at 12 hours after single intraperitoneal injection; while reduced the low density lipoprotein (LDL) level to 13, 28 and 86%, respectively in AIDRs. The maximum reduction 87% was observed by cucumber extract. Cucumber, white pumpkin and ridge gourd extracts reduced total cholesterol level to 29, 15 and 38%, respectively comparing with the diabetic control group. Here the maximum reduction of 85% was observed by white pumpkin extract. Cucumber, white pumpkin and ridge gourd also reduced triglyceride levels to 72, 68 and 80%, respectively. Maximum reduction of 32% was observed by white pumpkin. Significant improvement of glycogenesis was also observed by ridge gourd extracts in AIDRs.© 2013 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v5i1.10252        J. Sci. Res. 5 (1), 161-170 (2013)


2013 ◽  
Vol 39 (1) ◽  
pp. 6-10
Author(s):  
SMMMA Hasan ◽  
MI Khan ◽  
BU Kumar ◽  
MZ Sadeque

The study was performed to compare the blood glucose lowering effect of Swietenia mahagoni seeds with an oral antidiabetic drug, rosiglitazone in experimentally induced diabetic rats. Twentyfour healthy Long Evans Norwegian strain of rats were included in the study and divided into four groups (A, B, C and D) comprising 6 rats each. Group A (control group) received standard rat food for 14 days. Diabetes was induced by a single intraperitoneal administration of alloxan 120mg/kg body weight in Group B, C and D. Group B was given standard food for 10 days and considered as diabetic control. Group C and D were treated with ethanolic extract of Swietenia mahagoni seeds 1000mg/kg and rosiglitazone 10mg/kg orally respectively. Administration of ethanolic extract of Swietenia mahagoni seeds in group C and rosiglitazone in group D produced a significant reduction in blood glucose level as compared to diabetic control (group B). Histological examination of pancreas showed destruction of beta cells in Islets of pancreas in group B whereas retaining of islets and few degranulations of beta cells of pancreas found in group C and group D. The observations and results of the present study provide information that ethanolic extract of Swietenia mahagoni seeds has hypoglycaemic effect in experimentally induced diabetic rats which requires further investigation. DOI: http://dx.doi.org/10.3329/bmrcb.v39i1.15790 Bangladesh Med Res Counc Bull 2013; 39: 6-10


Author(s):  
Soumya Prakash Rout ◽  
Durga Madhab Kar ◽  
Laxmidhar Maharana

<p>ABSTRACT<br />Context: Several species of the genus Annona were reported to have hypoglycemic properties and this makes Annona reticulata Linn. (Annonaceae)<br />an interesting plant for investigating its anti-hyperglycemic potential.<br />Objective: Different fractions prepared from hydro-alcoholic extract of A. reticulata leave were investigated for their blood glucose lowering effect on<br />Streptozotocin (STZ) induced hyperglycemic rats.<br />Methods: Ethyl acetate, methanol, and residual fractions (at dose level of 100 mg/kg by oral route) prepared from the hydro-alcoholic extract of<br />A. reticulata leave were administered for 14 consecutive days to STZ induced hyperglycemic rats for evaluation of their anti-hyperglycemic potential.<br />Anti-hyperglycemic potential was assessed by observation of a decrease in fasting blood glucose level.<br />Results: The studies revealed that ethyl acetate fraction decreased the blood glucose level of hyperglycemic rats from 447.67 to 234.17 mg/dL and is<br />significant (p&lt;0.001) when compared with diabetic control group. The residual fraction and methanolic fraction decreased blood glucose level from<br />417.83 to 402.50 mg/dL and 432.33 to 371.67 mg/dL respectively but not significant when compared with the diabetic control group. Standard drug<br />metformin (dose 300 mg/kg) reduced the blood glucose level from 447.33 to 219.50 mg/dL.<br />Discussion: Ethyl acetate fraction at tested dose level was capable not only to control the elevated blood glucose level but also able to attenuate<br />certain secondary parameters associated with STZ induced hyperglycemia.<br />Conclusion: This study suggested that the ethyl acetate fraction prepared from hydro-alcoholic extract of A. reticulata leave exhibit potential antihyperglycemic<br />property<br />in the tested<br />experimental<br />models and should be investigated<br />further.<br />Keywords: Streptozotocin, Diabetes, Dyslipidemia.</p>


2017 ◽  
Vol 41 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Kun Zhang ◽  
Wei Song ◽  
Dalin Li ◽  
Jingqiang Yan ◽  
Yunhui Chen ◽  
...  

Background and aims: Cholesterol crystals have been shown to cause inflammation. As a response to cholesterol crystal accumulation, the NLRP3 inflammasome is activated to produce IL-1β which eventually leads to atherosclerotic lesions. As a part of innate immunity, CARD8 is involved in the modulation of above mentioned inflammatory activities. The primary objective of this study was to investigate the association between polymorphism of CARD8 rs2043211 and susceptibility to arteriosclerosis obliterans (ASO) in Chinese Han male population. Methods: 758 male arteriosclerosis obliterans patients and 793 male controls were genotyped for rs2043211 with the TaqMan allele assays. Fasting blood-glucose (FBG), total cholesterol (TC), triglycerides (TG), urea nitrogen, creatinine, Serum uric acid, high density lipoprotein, low density lipoprotein, ALT, AST, and IL-1β in the blood were detected for all subjects. Clinical data were recorded to analyze the genotype-phenotype. Independent samples t-test was used to perform the comparisons between two groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to measure the strength of relationship in the genotype distribution and allele frequencies between patients and controls. The analysis of variance was used for a genotype-phenotype analysis of the ASO patients. Results: The genotypic and allelic frequencies in the ASO group were significantly different from that in the control group (P = 0.014 by genotype, P = 0.003 by allele). Those carrying the genotype TT had a higher risk for ASO than those carrying the genotype AA (OR = 1.494, 95%CI1.131-1.974, P = 0.005).The difference was also significant after the adjustment for the history of smoking, TC, LDL, fasting blood glucose, systolic blood pressure and BMI(OR = 1.525, 95%CI1.158-2.009, P = 0.003). Conclusion: Our finding suggests that the polymorphism of CARD8 rs2043211 is probably associated with the development of ASO in Chinese Han male population.


2019 ◽  
Vol 30 (Number 1) ◽  
pp. 26-29
Author(s):  
S Sultana ◽  
N Y Mili ◽  
R Afroz ◽  
S Parveen

The experimental animal study was undertaken to investigate the preventive role ginger juice against hyperglycemia in alloxan induced diabetic rats.Male wistar rats,(130-150)gm wt fed on standard diet and water ad libitum, were divided into 3 groups(n=6) in each group: Group-L non-diabetic control group, Group-II, diabetic control & Group-III, normal rats pretreated with ginger before they were made diabetics. Diabetes was induced by inj. alloxan 150mg/kg body wt.,tp (Group-IL on 2nd day & Group-Ill, on the 9th day).Rats having blood glucose level of more than 7mmol/L on day 5(72 hours after alloxan inj) were considered diabetic & selected for experiment. Rats of Group-Ill received Zingiber officinale (ginger juice) (4m1/kg.body,wt orally) for 7 days (day 2-day8) through Pyles tube before alloxan induction & 3days after the induction. On day 12, animals were sacrificed under light ether anaesthesia, blood was collected by cardiac puncture for blood glucose estimation. Pretreatment with Zingiber officinale (ginger) juice significantly (p<0.01) reduced alloxan induced hyperglycemia.Zingiber officinale (ginger) is one of the most widely used spices and is reputed to have medicinal properties against diabetes mellitus. This study suggests that pretreatment with Zingiber officinale(ginger) prevents the development of hyperglycemia in alloxan induced diabetic rats.


Author(s):  
Padmaja Shetty K. ◽  
Pushpa V. H.

Background: Diabetes mellitus is a multifactorial metabolic disorder with several microvascular and macrovascular complications. Several plants have been used as dietary adjuvants to conventional drug therapy. Garcinia indica exhibits significant hypolipidemic and hypoglycemic activity. This study was conducted to evaluate the hypoglycemic effects of methanolic extract of seeds of Garcinia indica on blood glucose levels in Streptozotocin induced diabetic albino rats.Methods: Five groups of wistar albino rats (n=6) weighing 150-200g of either sex aged 3-4 months were obtained for the study. After overnight fasting, streptozotocin (50mg/kg) was administered intraperitoneally to induce diabetes. Five groups are: Group-1: Non diabetic control group, Group-2: diabetic control, Group-3: diabetic standard, Group-4: test group, Group-5: half of test + half of standard. Fasting blood sugar was estimated on 1, 3, 7, 14 and 28th day by capillary blood glucose method. The data obtained were subjected to statistical analysis.Results: In this study, following Streptozotocin administration the blood glucose levels increased in all groups on day 0. In group 2, blood glucose level gradually increased to 445.6±1.75mg/dl over a period of 4 weeks. Following glibenclamide administration in Group 3 - there was a gradual reduction in blood glucose levels: 269.8mg/dl - day 7 to 101.8mg/dl - week 4. Group 4 - persistent and significant (p<0.05) fall in blood glucose levels reaching upto 107mg/dl at the end of 4 weeks. Group 5 - 330mg/dl on day 1 which significantly (p<0.05) reduced to 101mg/dl on day 28. There was improvement in weight in group 4 and group 5 diabetic rats.Conclusions: The extract alone and in combination with glibenclamide showed significant hypoglycemic activity in comparison to diabetic control group.


Author(s):  
Khidir A. M. Hassan ◽  
Mahmoud M. E. Mudawi ◽  
Mansour I. Sulaiman

Metformin is now being recognized as the standard therapy in T2D patients who are overweight. Metformin has many drug-disease interactions that can increase the risk of metformin-associated lactic acidosis. Therefore this study was conducted to evaluate any possible pharmacodynamic interactions between metformin and drugs used to treat chronic diseases e.g. Hypertension. The rats were fasted overnight before inducing diabetes with streptozotocin. The rats were given an intraperitoneal injection of streptozotocin (50 mg kg−1) freshly prepared in 0.1M sodium citrate buffer. The diabetic state was confirmed 72 h after streptozotocin injection. Diabetic rats were grouped into seven groups each group of five rats and distributed among the normal control group diabetic control group and the treatment groups. The treatment continued for 10 days. Blood samples were taken before treatment and after 10 days and analyzed for serum glucose, cholesterol, HDL, LDL, and triglycerides. In the diabetic control group which was given STZ alone the blood glucose level decreased significantly (p &lt; 0.05) after 10 days but still above the hyperglycemic level (200mg/dl). The same was observed in the group treated with metformin. The group treated with nifedipine and aspirin showed significant reduction (p &lt; 0.01) in the glucose level below the hyperglycemic level (200mg/dl). While the groups treated with (Metformin + Nifedipine) and (Metformin +Aspirin) showed highly significant reduction (P&lt;0.001) in blood glucose level. These results conclude that the combination of (metformin +Nifedipine) and the combination of (Metformin + Aspirin) have highly significant hypoglycemic effect. It also showed that Nifedipine has promising role in reducing blood glucose level, lipid profile especially LDL-cholesterol, and body weight.


Author(s):  
Devita Anggraeni ◽  
Claude Mona Airin ◽  
Slamet Raharjo

This research aimed to study the effectiveness of ethanol extract of binahong leaves on blood glucose, insulin, blood chemical profiles (serum glutamic pyruvate transaminase=SGPT, serum glutamic oxaloacetic transaminase=SGOT, ureum, and creatinine), and skin histopathology in diabetic rat. A total of 20 male Wistar rats aged 3 months (± 250 gram) were divided into five groups, with four rats in each group. Group I (non-diabetic control) was injected with 0.1 M sodium citrate buffer, while group II (diabetic control), III, IV, and V were injected with single dose of Streptozotocin (STZ) at dose 40 mg/kg intraperitoneally (IP). One week after the injection, the dorsal skin of the rats were excised. Group I and II were given cream topically and 1% NaCMC orally, group III was given 50% ethanol extract of binahong leaves (EEB) topically and 1% NaCMC orally, group IV was given cream topically and EEB 300 mg/kg orally, and group V was given 50% EEB topically and EEB 300 mg/kg orally. These treatments were continued for 14 days. Blood samples were obtained at the end of study to examine blood glucose, insulin, and blood chemical profiles (SGOT, SGPT, ureum, and creatinine). Examination of skin histopathology and leukocyte count were also done. The result showed that blood glucose, insulin, SGOT, SGPT, and ureum level of diabetic rats given topical or oral EEB did not significantly different from diabetic control group, even though blood glucose, insulin, SGOT, SGPT, and ureum level of diabetic rats given topical and oral EEB were found lower compared to diabetic control group. Administration of EEB 300 mg/kg orally in diabetic rats could lower creatinine level significantly (P<0.05). Histopathological examination of dorsal skin of diabetic rats which were given EEB topically showed the decrease of fibroblast proliferation, leukocyte infiltration, and hemorrhage in dermis area. Leukocyte count on skin tissue was significantly lower (P<0.05) in diabetic rats given EEB. In conclusion, topical or oral administration of EEB can help healing process in diabetic wound.


Author(s):  
OLUSAYO A SHORINWA ◽  
GORDON EI EMENU

Objectives: This study investigated the antidiabetic and antihyperlipidemic potential of the ethanol extract of the leaves and stem of Cissus gracillis on alloxan monohydrate-induced diabetic albino rats. Methods: Preliminary phytochemical screening and acute toxicity were carried out. Animals were assigned into seven groups of five rats each. Groups A and B were administered 10 mg/kg each of glibenclamide and atorvastatin respectively, C, D, and E were given 125, 250 and 500 mg/kg of ethanol extract of C. gracillis, respectively, daily for 21 days through oral gavage, group F was diabetic but untreated (diabetic control group), while group G was non-diabetic and untreated which served as the control group. Results: Phytochemical screening revealed the presence of steroids/triterpenoids and carbohydrates. LD50 was above 5000 mg/kg. The extract at 500 mg/kg showed a statistically significant (p<0.05) decrease in blood glucose level when compared with the glibenclamide group on day 21. However, gradual non- significant reduction in blood glucose levels were observed in the extract treated groups on the 7th, 14th, and 21st days of treatment. The administration of ethanol extract of C. gracillis to alloxan-induced diabetic rats produced a decrease in total cholesterol, triglycerides, and low-density lipoproteins comparable to glibenclamide and atorvastatin. Conclusion: The ethanol extract of the leaves and stem of C. gracillis possess a mildly significant antidiabetic and antihyperlipidemic activity.


2009 ◽  
Vol 37 (02) ◽  
pp. 361-372 ◽  
Author(s):  
Ming Xiang ◽  
Jing Tang ◽  
Xiao-Lei Zou ◽  
Zeng-Yu Zhao ◽  
Yun-Yang Wang ◽  
...  

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic β cells and CD4+ T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer β cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4+ T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and β cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected β cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4+ T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.


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