scholarly journals Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy

2020 ◽  
Vol 21 (17) ◽  
pp. 6243 ◽  
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Yukihiro Miwa ◽  
Xiaoyan Jiang ◽  
Masayuki Ohta ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Glucose ◽  
Vision Loss ◽  
Early Stage ◽  
Neural Function ◽  
Peroxisome Proliferator ◽  
Diabetic Mice ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Adult Mice

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

scholarly journals Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy

2021 ◽  
Vol 10 (20) ◽  
pp. 4666
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Kazuo Tsubota ◽  
Kazuno Negishi ◽  
Toshihide Kurihara
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Vascular Endothelial Cells ◽  
Vitreous Hemorrhage ◽  
Diabetic Animal ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Anti Vegf

Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments.

scholarly journals Purified Gymnemic Acids from Gymnema inodorum Tea Inhibit 3T3-L1 Cell Differentiation into Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2851
Author(s):  
Papawee Saiki ◽  
Yasuhiro Kawano ◽  
Takayuki Ogi ◽  
Prapaipat Klungsupya ◽  
Thanchanok Muangman ◽  
...  
Keyword(s):  
Early Stage ◽  
Uncoupling Protein ◽  
Glucose Absorption ◽  
Mitochondrial Activity ◽  
Peroxisome Proliferator ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Medicinal Properties

Gymnema inodorum (GI) is an indigenous medicinal plant and functional food in Thailand that has recently helped to reduce plasma glucose levels in healthy humans. It is renowned for the medicinal properties of gymnemic acid and its ability to suppress glucose absorption. However, the effects of gymnemic acids on adipogenesis that contribute to the accumulation of adipose tissues associated with obesity remain unknown. The present study aimed to determine the effects of gymnemic acids derived from GI tea on adipogenesis. We purified and identified GiA-7 and stephanosides C and B from GI tea that inhibited adipocyte differentiation in 3T3-L1 cells. These compounds also suppressed the expression of peroxisome proliferator-activated receptor gamma (Pparγ)-dependent genes, indicating that they inhibit lipid accumulation and the early stage of 3T3-L1 preadipocyte differentiation. Only GiA-7 induced the expression of uncoupling protein 1 (Ucp1) and pparγ coactivator 1 alpha (Pgc1α), suggesting that GiA-7 induces mitochondrial activity and beige-like adipocytes. This is the first finding of stephanosides C and B in Gymnema inodorum. Our results suggested that GiA-7 and stephanosides C and B from GI tea could help to prevent obesity.

scholarly journals CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis

2017 ◽  
Vol 37 (14) ◽  
Author(s):  
Hyunbae Kim ◽  
Ze Zheng ◽  
Paul D. Walker ◽  
Gregory Kapatos ◽  
Kezhong Zhang
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels

ABSTRACT Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress.

scholarly journals Sea grapes extract improves blood glucose, total cholesterol, and PGC-1α in rats fed on cholesterol- and fat-enriched diet

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 718
Author(s):  
Mury Kuswari ◽  
Fahrul Nurkolis ◽  
Nelly Mayulu ◽  
Faisal Maulana Ibrahim ◽  
Nurpudji Astuti Taslim ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Total Cholesterol ◽  
Unsaturated Fatty Acids ◽  
Blood Cholesterol ◽  
Albino Rats ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phytochemical Content ◽  
Glucose Levels

Background: Sea grapes or  Caulerpa racemosa have a lot of phytochemical content, especially unsaturated fatty acids that are beneficial for health. This study aims to evaluate the effects of sea grapes extract on blood glucose levels, total cholesterol-, and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α in male Wistar rats, which were given per-oral (p.o.) cholesterol- and carbohydrates fat-enriched diets (CFED). Methods: Forty male Wistar albino rats weighing between 200 – 250 g were used for this study. Animals were randomly distributed into four groups of ten animals each. Group A served as control (received standard dry pellet diet). Rats in group B were fed on CFED for 4 weeks.  Groups C and D were fed on CFED and were administered 150 and 450 mg/kg of  sea grapes extract (p.o.), respectively. Results: Group C rats indicated a blood glucose reduction and an increase in PGC-1α serum, in comparison to group D (p<0.05). There were no significant differences between group C and D in blood cholesterol reduction (high dose of the extract did not have significant effects) (p=0.222), and both groups had the same effect in lowering total cholesterol in rats. Conclusion: Sea grapes extract is proven to improve blood glucose, total cholesterol, and PGC-1α levels in rats fed with CFED.

scholarly journals PPARα Agonist Oral Therapy in Diabetic Retinopathy

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 433
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Animal Studies ◽  
Early Stage ◽  
Vitreoretinal Surgery ◽  
Global Scale ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.

scholarly journals The Effect of Gembili Starch (Dioscorea esculenta) and Eubacterium rectal Supplementation on Skeletal Muscle Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (Pgc-1α) Expression in Diabetic Mice Models

2021 ◽  
Vol 9 (A) ◽  
pp. 1061-1067
Author(s):  
Tri Setyawati ◽  
Rio Jati Kusuma ◽  
Harry Freitag Luglio ◽  
Neni Oktiyani ◽  
Sunarti Sunarti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Diabetic Control ◽  
Peroxisome Proliferator ◽  
Diabetic Mice ◽  
Transcriptional Coactivator ◽  
Control Groups ◽  
Peroxisome Proliferator Activated Receptor ◽  
Before And After ◽  
Dividing Cells

BACKGROUND: Gembili or Dioscorea esculenta is a local food that is produced by several areas in Indonesia. Few studies have reported its health benefits for diabetes mellitus but a little is understood about its mechanism of action. PGC-1α is a transcriptional coactivator for genes that involved in energy metabolism and increased expression of this gene has previously been associated with improved insulin sensitivity. AIM: The objective of this study was to investigate the effect of Gembili starch and Gembili starch with butirogenic bacteria Eubacterium rectal on PGC-1α expression in skeletal muscle of diabetic mice. MATERIALS AND METHODS: Three months old male diabetic Wistar mice were divided into groups based on dietary supplement: Gembili starch only; Gembili starch with E. rectal; and E. rectal only. Positive (diabetic mice) and negative (non-diabetic) control groups were used in this study. After 4 weeks of supplementation, mice were sacrificed and muscle tissue was taken from musculus vastus latissimus. Plasma blood glucose was measured before and after intervention. PGC-1α expression was measured with immunohistochemistry and quantified by dividing cells that produce PGC-1α with total cells. RESULTS: Plasma blood glucose was reduced after invention in group that received Gembili starch only (p < 0.001); Gembili starch with E. rectal (p < 0.001); and E. rectal only (p < 0.001). The protein expression of PGC-1α in diabetic mice receiving Gembili starch only was significantly higher compared to control (p < 0.05). CONCLUSION: This study shown that Gembili starch supplementation was able to improve glucose control in diabetic mice and this effect was obtained perhaps through PGC-1α activation. Further study is needed to investigate the effect of Gembili starch supplementation on fat metabolism.

scholarly journals Sea grapes extract improves blood glucose, total cholesterol, and PGC-1α in rats fed on cholesterol- and fat-enriched diet

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 718
Author(s):  
Mury Kuswari ◽  
Fahrul Nurkolis ◽  
Nelly Mayulu ◽  
Faisal Maulana Ibrahim ◽  
Nurpudji Astuti Taslim ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Total Cholesterol ◽  
Unsaturated Fatty Acids ◽  
Blood Cholesterol ◽  
Albino Rats ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phytochemical Content ◽  
Glucose Levels

Background: Sea grapes or  Caulerpa racemosa have a lot of phytochemical content, especially unsaturated fatty acids that are beneficial for health. This study aims to evaluate the effects of sea grapes extract on blood glucose levels, total cholesterol-, and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α in male Wistar rats, which were given per-oral (p.o.) cholesterol- and carbohydrates fat-enriched diets (CFED). Methods: Forty male Wistar albino rats weighing between 200 – 250 g were used for this study. Animals were randomly distributed into four groups of ten animals each. Group A served as control (received standard dry pellet diet). Rats in group B were fed on CFED for 4 weeks.  Groups C and D were fed on CFED and were administered 150 and 450 mg/kg of  sea grapes extract (p.o.), respectively. Results: Group C rats indicated a blood glucose reduction and an increase in PGC-1α serum, in comparison to group D (p<0.05). There were no significant differences between group C and D in blood cholesterol reduction (high dose of the extract did not have significant effects) (p=0.222), and both groups had the same effect in lowering total cholesterol in rats. Conclusion: Sea grapes extract is proven to improve blood glucose, total cholesterol, and PGC-1α levels in rats fed with CFED.

scholarly journals Comparative Study of 3 Different Brands of Glimperide

2020 ◽  
Keyword(s):  
Blood Glucose ◽  
Ppar Gamma ◽  
Dissolution Time ◽  
Peroxisome Proliferator ◽  
Disintegration Time ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Weight Variation

Glimepiride is an antidiabetic agent used for lowering blood glucose levels. It induces the activity of peroxisome proliferator-activated receptor-gamma (PPAR gamma). It lowers blood glucose levels by binding to ATP-sensitive potassium channel receptors on the surface of pancreatic cells. The purpose of this study was to perform a comparative analysis of different physicochemical parameters (weight variation, hardness, thickness, friability, disintegration time, and dissolution time) of 3 different commercially available brands of glimepiride in the market. Statistical analysis revealed minor variations in the results. It was found that GETRYL showed the highest % dissolution among all the 3 brands whereas AMARYL took the least time to disintegrate. According to the results of the friability test, Diabold shows the highest stability in the friabilator. However, all 3 brands complied with the official pharmacopoeial limits. The quality of the drug largely influences its therapeutic activity. Hence, owing to the similar physicochemical profile, all the 3 brands can be interchangeably used.

scholarly journals The effect of vitamin K1 on VEGF levels in chick embryos with type 1 diabetes and Diabetic Retinopathy induced by streptozotocin

2021 ◽  
Vol 8 (9) ◽  
pp. 551-555
Author(s):  
Erhan Bozkurt ◽  
Emre Atay ◽  
Oğuz Han Koca ◽  
Mehmet Cem Sabaner
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Glucose ◽  
Growth Factor ◽  
Early Stage ◽  
Vitamin K1 ◽  
Chick Embryos ◽  
Blood Insulin ◽  
Glucose Levels ◽  
Specific Pathogen ◽  
Endothelial Growth Factor

Objective: Hyperglycemia caused by Diabetes Mellitus (DM) is associated with long-term dysfunction such as diabetic retinopathy (DRP). The most effective growth factor in the development of DRP is the vascular endothelial growth factor (VEGF). Vitamin K1 reduces hyperglycemia and prevents the development of DM. In this study, we aimed to create streptozotocin (STZ) induced DM and DRP in chick embryos and to show whether vitamin K1 can prevent early-stage DRP by measuring VEGF levels. Material and Methods: The 140 specific pathogen-free (SPF) fertilized chicken eggs were used in this study. Three different STZ doses were administered to 120 SPF eggs for an induced DM model. Three different vitamin K1 doses were administered in each STZ dose group. On the 12th day and 18th day the remaining 20 SPF eggs were separated as control groups. On the 18th-day, blood glucose, blood insulin and VEGF levels were measured. Results: 0.45 mg/egg STZ dose (STZ3) was determined as the optimal/ideal dose for the DM model. When the group-administered STZ3 and vitamin K1 were evaluated among themselves; it was determined that there were significant changes in blood glucose, blood insulin, VEGF levels of the STZ3+K1-3 group compared to the STZ3+K1-1 and STZ3+K1-2 groups (p<0.05). Conclusion: Vitamin K1 increases blood insulin levels and decreases blood glucose levels. When hyperglycemia reduces, the VEGF levels reduce. Vitamin K1 protects from DRP by reducing VEGF levels.

scholarly journals Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

2012 ◽  
Vol 26 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Kristin A. Anderson ◽  
Fumin Lin ◽  
Thomas J. Ribar ◽  
Robert D. Stevens ◽  
Michael J. Muehlbauer ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

Abstract Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

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