Amelioration of glucose homeostasis by glycyrrhizic acid through gluconeogenesis rate-limiting enzymes

Chia, Yoke Yin; Liong, Shih Yeen; Ton, So Ha; Kadir, Khalid Bin Abdul

doi:10.1016/j.ejphar.2011.12.037

Cited by 20 publications

(19 citation statements)

References 24 publications

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“…Therefore, it is possible that increased glucose‐6‐phosphate originating from glucose uptake might be used as a source of lipid synthesis rather than glycogen synthesis. The expression of gluconeogenesis‐related factors was also confirmed, but the expression of PEPCK, which acts as a rate‐limiting enzyme in the early stage (Chia, Liong, Ton, & Kadir, ), was significantly reduced. Finally, when GLUT2 was knocked down, there was no increase in acetyl‐CoA level due to H 2 O 2 treatment, indicating that increased fat synthesis occurred through increased glucose uptake by ROS.…”

Section: Discussionmentioning

confidence: 91%

Reactive oxygen species‐induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging

et al. 2019

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Aging is a major risk factor for many chronic diseases due to increased vulnerability to external stress and susceptibility to disease. Aging is associated with metabolic liver disease such as nonalcoholic fatty liver. In this study, we investigated changes in lipid metabolism during aging in mice and the mechanisms involved. Lipid accumulation was increased in liver tissues of aged mice, particularly cholesterol. Increased uptake of both cholesterol and glucose was observed in hepatocytes of aged mice as compared with younger mice. The mRNA expression of GLUT2, GK, SREBP2, HMGCR, and HMGCS, genes for cholesterol synthesis, was gradually increased in liver tissues during aging. Reactive oxygen species (ROS) increase with aging and are closely related to various aging‐related diseases. When we treated HepG2 cells and primary hepatocytes with the ROS inducer, H2O2, lipid accumulation increased significantly compared to the case for untreated HepG2 cells. H2O2 treatment significantly increased glucose uptake and acetyl‐CoA production, which results in glycolysis and lipid synthesis. Treatment with H2O2 significantly increased the expression of mRNA for genes related to cholesterol synthesis and uptake. These results suggest that ROS play an important role in altering cholesterol metabolism and consequently contribute to the accumulation of cholesterol in the liver during the aging process.

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Section: Discussionmentioning

confidence: 91%

Reactive oxygen species‐induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging

et al. 2019

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“…They suggested that this effect may be due to inhibition of hepatic glucose production. Also, Chia et al (2012) showed that treatment by glycyrrhetinic acid, the aglycone derivative of glycyrrhizinic acid, led to blood glucose levels being decreased in STZ-diabetic rats. Consistent with the present study, earlier studies have reported the effects of betulinic acid on high fat diet-induced diabetic mice (Kim et al, 2014) and by oleanolic acid in STZ-diabetic mice (Gao et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…The results show that treatment with BA in STZ-NA diabetic mice decreased HOMA-IR compared with the control group. Also, Chia et al (2012) showed that treatment with glycyrrhizinic acid (a triterpenoid of the ursane group) decreased HOMA-IR due to a decrease in the gluconeogenesis ratelimiting enzymes. Consistent with our study, treatment with betulin improved insulin sensitivity (Tang et al, 2011).…”

Section: Effects Of Stz-na Metformin and Ba Treatment On Insulin Andmentioning

confidence: 99%

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

Birgani

Ahangarpour

Khorsandi

et al. 2018

Braz. J. Pharm. Sci.

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Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group.

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“…According to Glavac and Kreft [12], after oral ingestion of 600 mg of glycyrrhizin in human subjects, the metabolites appear in urine ranging from 1.5 to 14 h and can be detected in the urine even after 4 days. Protection of liver cells from experimentally induced metabolic disorders and hepatocellular injury by glycyrrhizin has been reported in different publications [13][14][15][16][17][18][19]. Antidiabetic effect of glycyrrhizin and its metabolite 18b-glycyrrhetinic acid has been reported in streptozotocin-induced type 1 diabetes mellitus in rat model [20,21].…”

Section: Introductionmentioning

confidence: 98%

Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model

2015

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Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome.

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Amelioration of glucose homeostasis by glycyrrhizic acid through gluconeogenesis rate-limiting enzymes

Cited by 20 publications

References 24 publications

Reactive oxygen species‐induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging

Reactive oxygen species‐induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model

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