Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice

Nerurkar, Pratibha V.; Nishioka, Adrienne; Eck, Philip; Johns, Lisa M; Volper, Esther M.; Nerurkar, Vivek R.

doi:10.1017/s0007114511005563

Cited by 45 publications

(37 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32,33) In the liver, FoxO1 is responsible for the activation of gluconeogenesis by the transcriptional activation of gluconeogenic genes. [34][35][36] As shown in Fig. 2, geniposide phosphorylated FoxO1 in dose-dependent manners.…”

Section: Fig 1 Effect Of Geniposide On Glucose Production In Hepg2 mentioning

confidence: 99%

Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells

Guo

Zheng

Liu

et al. 2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPKα expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK-FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis.Key words geniposide; hepatic glucose production; AMP-activated protein kinase; HepG2 cell Type 2 diabetes mellitus (T2DM) comprises heterogeneous disorders that result in chronic hyperglycemia and lifethreatening complications. The pathological change in hepatic glucose production is a central characteristic in diabetic patients.1) Hyperglycemia in both types 1 and 2 diabetes mellitus is associated with high hepatic glucose production.2) Suppression of hepatic glucose production has been shown to improve overall glycemic control in both human patients and type 2 diabetes animal models.3) The control of hepatic glucose production depends on many factors, including the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), insulin levels, and the concentration of gluconeogenic substrates (lactate, gluconeogenic amino acids, and glycerol). A variety of molecular signaling pathways were demonstrated to regulate hepatic glucose production, such as AMP-activated protein kinase (AMPK) activation, 4) protein kinase B (AKT or PKB) phosphorylation and mitogen-activated protein kinase (MAPK) inhibition. Among them, AMPK, the evolutionarily conserved serine/threonine kinase, is considered as the major signaling molecule responsible for this process. AMPK acts as an intracellular sensor to maintain the glucose homeostasis in the hypothalamus, skeletal muscle and liver [5][6][7] by the phosphorylation of several downstream metabolic enzymes and certain transcription factors. In the liver, the acute activation of AMPK, achieved by adenovirus-mediated gene transfer of a co...

show abstract

Section: Fig 1 Effect Of Geniposide On Glucose Production In Hepg2 mentioning

confidence: 99%

Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells

Guo

Zheng

Liu

et al. 2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…In the present study, it was not observed difference in fasting glucose between groups. In turn, Nerurkar et al (2012) found that fermented noni juice was able to improve glucose metabolism in rats fed a diet rich in lipids by regulating of FoxO1. In diabetic rats, noni was also benefit by modulation of PPAR-γ receptor and AMPK (Lee et al, 2012).…”

Section: Discussionmentioning

confidence: 97%

Effects of Consumption of Noni (Morinda citrifolia) in Rats Fed a High-Fat Diet

Machado¹,

Sousa²,

Montenegro³

et al. 2016

IJMP

View full text Add to dashboard Cite

Objective: To evaluate the effects of noni consumption on risk factors for cardiovascular disease, fasting glucose and hepatic and renal function in rats fed a high-fat diet. Methods: 18 Wistar rats were divided into three groups. Group control (C) was fed with high-fat diet and water. Group's noni juice (NJ) and noni infusion (NI) received the same diet and noni juice and infusion, respectively, for 4 weeks. After this time were assessed anthropometric measurements, adiposity, organ weights and biochemical measurements. Results: Groups NJ and NI had higher waist circumference compared to group C (C=11.0 cm, NJ=12.8 cm and NI=14.0 cm, p<0.05), lower serum creatinine (C=0.8 mg/dL, NJ=0.2 mg/dL and NI=0.3 mg/dL, p<0.05), and higher blood urea nitrogen/creatinine ratio (C=92.7, NJ=349.3 and NI=230.4, p<0.05). Noni infusion consumption promoted higher serum total cholesterol (C=59.7 mg/dL, NJ=60.1 mg/dL and NI=99.8 mg/dL, p<0.05) and LDL (C=48.5 mg/dL, NJ=42.0 mg/dL and NI=78.7 mg/dL, p<0.05). Conclusion: Consumption of noni, either as juice or as infusion, promoted higher waist circumference and blood urea nitrogen/creatinine ratio. Furthermore, noni infusion consumption promoted increased of serum total cholesterol and LDL

show abstract

“…The plant is of common and ancient use in the Pacific; "Noni" preparations have been commercialized in the USA since the 1990s and are increasingly distributed all over the world. This plant inhibits gluconeogenic genes in animal studies (Nerurkar et al, 2012). It would be also interesting to compare different preparations, such as the commercial juice and the locally prepared decoctions.…”

Section: Discussionmentioning

confidence: 99%