scholarly journals Peroxisome Proliferator-activated Receptor α (PPARα) Influences Substrate Utilization for Hepatic Glucose Production

2002 ◽  
Vol 277 (52) ◽  
pp. 50237-50244 ◽  
Author(s):  
Jun Xu ◽  
Gary Xiao ◽  
Chuck Trujillo ◽  
Vicky Chang ◽  
Lilia Blanco ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Substrate Utilization ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Glucose

Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia

2006 ◽  
Vol 291 (3) ◽  
pp. E536-E543 ◽  
Author(s):  
Chaodong Wu ◽  
Salmaan A. Khan ◽  
Li-Jen Peng ◽  
Honggui Li ◽  
Steven G. Carmella ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Flux ◽  
Hepatic Glucose

Hepatic insulin resistance is one of the characteristics of type 2 diabetes and contributes to the development of hyperglycemia. How changes in hepatic glucose flux lead to insulin resistance is not clearly defined. We determined the effects of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P2), a key regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice. Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P2 level, hepatic F26P2 levels were decreased twofold compared with those of control virus-treated mice in basal state. In addition, under hyperinsulinemic conditions, hepatic F26P2 levels were much lower than those of the control. The decrease in F26P2 leads to the elevation of basal and insulin-suppressed hepatic glucose production. Also, the efficiency of insulin to suppress hepatic glucose production was decreased (63.3 vs. 95.5% suppression of the control). At the molecular level, a decrease in insulin-stimulated Akt phosphorylation was consistent with hepatic insulin resistance. In the low hepatic F26P2 states, increases in both gluconeogenesis and glycogenolysis in the liver are responsible for elevations of hepatic glucose production and thereby contribute to the development of hyperglycemia. Additionally, the increased hepatic gluconeogenesis was associated with the elevated mRNA levels of peroxisome proliferator-activated receptor-γ coactivator-1α and phospho enolpyruvate carboxykinase. This study provides the first in vivo demonstration showing that decreasing hepatic F26P2 levels leads to increased gluconeogenesis in the liver. Taken together, the present study demonstrates that perturbation of glucose flux in the liver plays a predominant role in the development of a diabetic phenotype, as characterized by hepatic insulin resistance.

scholarly journals Increased Hepatic Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Rat Model of Intrauterine Growth Retardation and Subsequent Insulin Resistance

Endocrinology ◽  
2002 ◽  
Vol 143 (7) ◽  
pp. 2486-2490 ◽  
Author(s):  
Robert H. Lane ◽  
Nicole K. MacLennan ◽  
Jennifer L. Hsu ◽  
Sara M. Janke ◽  
Tho D. Pham
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intrauterine Growth ◽  
Hepatic Glucose

Abstract Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of type 2 diabetes in humans and rats. Unsuppressed endogenous hepatic glucose production is a common component of the insulin resistance associated with type 2 diabetes. Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) mediates hepatic glucose production by controlling mRNA levels of glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1,6-bisphosphatase (FBPase). We therefore hypothesized that gene expression of PGC-1 would be increased in juvenile IUGR rat livers, and this increase would directly correlate with hepatic mRNA levels of PEPCK, G-6-Pase, and FBPase, but not glucokinase. We found that IUGR hepatic PGC-1 protein levels were increased to 230 ± 32% and 310 ± 47% of control values at d 0 and d 21 of life, respectively. Similarly, IUGR hepatic PGC-1 mRNA levels were significantly elevated at both ages. Concurrent with the increased PGC-1 gene expression, IUGR hepatic mRNA levels of G-6-Pase, PEPCK, and FBPase were also significantly increased, whereas glucokinase mRNA levels were significantly decreased. These data suggest that increased PGC-1 expression and subsequent hepatic glucose production contribute to the insulin resistance observed in the IUGR juvenile rat.

scholarly journals Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5

2010 ◽  
Vol 205 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Paul W Caton ◽  
Nanda K Nayuni ◽  
Julius Kieswich ◽  
Noorafza Q Khan ◽  
Muhammed M Yaqoob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mechanism Of Action ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peroxisome Proliferator ◽  
Hepatic Gluconeogenesis ◽  
Gene Target ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nicotinamide Phosphoribosyltransferase

Abnormal elevation of hepatic gluconeogenesis is central to the onset of hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). Metformin corrects hyperglycaemia through inhibition of gluconeogenesis, but its mechanism of action is yet to be fully described. SIRT1 and GCN5 (listed as KAT2A in the MGI Database) have recently been identified as regulators of gluconeogenic gene expression through modulation of levels and activity of the coactivators cAMP-response element binding protein-regulated transcription coactivator 2 (TORC2 or CRTC2 as listed in the MGI Database) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α or PPARGC1A as listed in the MGI Database). We report that in db/db mice, metformin (250 mg/kg per day; 7 days) increases hepatic levels of GCN5 protein and mRNA compared with the untreated db/db mice, as well as increases levels of SIRT1 protein and activity relative to controls and untreated db/db mice. These changes were associated with reduced TORC2 protein level and decreased gene expression and activation of the PGC1α gene target phosphoenolpyruvate carboxykinase, and lower plasma glucose and insulin. Inhibition of SIRT1 partially blocked the effects of metformin on gluconeogenesis. SIRT1 was increased through an AMP-activated protein kinase-mediated increase in gene expression of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme of the salvage pathway for NAD+. Moreover, levels of GCN5 were dramatically reduced in db/db mice compared with the controls. This indicates that loss of GCN5-mediated inhibition of gluconeogenesis appears to constitute a major mechanism for the onset of abnormally elevated hepatic glucose production in db/db mice. In conclusion, induction of GCN5 and SIRT1 potentially represents a critical mechanism of action of metformin. In addition, these data identify induction of hepatic GCN5 as a potential therapeutic strategy for treatment of T2DM.

FoxO3 regulates hepatic glucose production

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
S Gul ◽  
KH Holzmann ◽  
F Leithäuser ◽  
H Maier ◽  
B Böhm ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

Hyperglycemia per se does not inhibit hepatic glucose production in man

1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S20
Author(s):  
M.J. MÜLLER ◽  
K.J. ACHESON ◽  
A. G. BURGER ◽  
E. JEQUIER ◽  
A. VON ZUR MÜHLEN
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose ◽  
Per Se

Regulation of Hepatic Glucose Production by Transforming Growth Factor Beta 1 via Protein Kinase A

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2441-PUB ◽  
Author(s):  
QUAN PAN ◽  
YUNMEI CHEN ◽  
HUI YAN ◽  
WANBAO YANG ◽  
ZHENG SHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose ◽  
Growth Factor Beta ◽  
Kinase A

64-LB: Aerobic Exercise Decreases Hepatic Glucose Production via Asprosin Pathway in Diabetic Rats

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 64-LB
Author(s):  
JEONGRIM KO ◽  
TAE NYUN KIM ◽  
DAE YUN SEO ◽  
JIN HAN
Keyword(s):  
Aerobic Exercise ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Diabetic Rats ◽  
Hepatic Glucose

The role of autoregulation of the hepatic glucose production in man. Response to a physiologic decrement in plasma glucose

Diabetes ◽  
1986 ◽  
Vol 35 (2) ◽  
pp. 186-191 ◽  
Author(s):  
I. Hansen ◽  
R. Firth ◽  
M. Haymond ◽  
P. Cryer ◽  
R. Rizza
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose
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