scholarly journals Fructose-Induced Hypothalamic AMPK Activation Stimulates Hepatic PEPCK and Gluconeogenesis due to Increased Corticosterone Levels

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3633-3645 ◽  
Author(s):  
Andrezza Kinote ◽  
Juliana A. Faria ◽  
Erika A. Roman ◽  
Carina Solon ◽  
Daniela S. Razolli ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Ampk Activation ◽  
Hepatic Gluconeogenesis ◽  
Compound C ◽  
Ampk Phosphorylation ◽  
Hepatic Glucose ◽  
Amp Activated Protein Kinase ◽  
Interfering Rna

Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5′-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPKα2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels.

Enhanced gluconeogenesis from lactate in perfused livers after endurance training

1993 ◽  
Vol 74 (2) ◽  
pp. 782-787 ◽  
Author(s):  
K. D. Sumida ◽  
J. H. Urdiales ◽  
C. M. Donovan
Keyword(s):  
Endurance Training ◽  
Hepatic Glucose Production ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis ◽  
Bicarbonate Buffer ◽  
Hepatic Glucose ◽  
14Co2 Production ◽  
Glucose Output ◽  
And Control

The effects of endurance training (running 90 min/day at 30 m/min, 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats with use of the isolated liver perfusion technique. After isolation, the liver was perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes (hematocrit 22–24%) with no added substrate. Subsequent to the "washout" period, the reservoir was elevated with various concentrations of lactate and [U-14C]lactate (10,000 dpm/ml) to assess hepatic glucose production. Relative flow rates were not significantly different between trained (1.94 +/- 0.05 ml/g liver) and control livers (1.91 +/- 0.05 ml/g liver). Furthermore, no significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from trained or control livers. At saturating arterial lactate concentrations (> 2 mM), the maximal rate (Vmax) for hepatic glucose production was significantly higher for trained (0.91 +/- 0.04 mumol.min-1 x g liver-1) than for control livers (0.73 +/- 0.02 mumol.min-1 x g liver-1). That this reflected increased gluconeogenesis is supported by a significant elevation in the Vmax for [14C]glucose production from trained (13,150 +/- 578 dpm.min-1 x g liver-1) compared with control livers (10,712 +/- 505 dpm.min-1 x g liver-1). Significant increases were also observed in the Vmax for lactate uptake (25%), O2 consumption (19%), and 14CO2 production (23%) from endurance-trained livers. The Km for hepatic glucose output, approximately 1.05 mM lactate, was unchanged after endurance training. These findings demonstrate that chronic physical activity results in an elevated capacity for hepatic gluconeogenesis, as assessed in situ at saturating lactate concentrations.

scholarly journals Current understanding of metformin effect on the control of hyperglycemia in diabetes

2016 ◽  
Vol 228 (3) ◽  
pp. R97-R106 ◽  
Author(s):  
Hongying An ◽  
Ling He
Keyword(s):  
Type 2 Diabetes ◽  
Mechanism Of Action ◽  
Insulin Signaling ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Ampk Activation ◽  
First Line ◽  
Hepatic Glucose

Metformin is a first-line oral anti-diabetic agent that has been used clinically to treat patients with type 2 diabetes for over 60 years. Due to its efficacy in therapy and affordable price, metformin is taken by more than 150 million people each year. Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling. However, its mechanism of action remains partially understood and controversial, especially in regard to the role of AMPK in metformin's action and the mechanism of AMPK activation. In this review, we discuss recent advances in the understanding of metformin's suppression of hepatic glucose production and the mechanism related to the improvement of insulin signaling.

scholarly journals Berberine Attenuates Hyperglycemia by Inhibiting the Hepatic Glucagon Pathway in Diabetic Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhong ◽  
Jing Jin ◽  
Peiyu Liu ◽  
Yu Song ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Intracellular Camp ◽  
Diabetic Mice ◽  
Hepatic Gluconeogenesis ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hepatic Glucose ◽  
Glucose Output

Dysregulated glucagon drives hyperfunction in hepatic glucose output, which is the main cause of persistent hyperglycemia in type 2 diabetes. Berberine (Zhang et al., 2010) has been used as a hypoglycemic agent, yet the mechanism by which BBR inhibits hepatic gluconeogenesis remains incompletely understood. In this study, we treated diabetic mice with BBR, tested blood glucose levels, and then performed insulin, glucose lactate, and glucagon tolerance tests. Intracellular cAMP levels in hepatocytes were determined by ELISA, hepatic gluconeogenetic genes were assayed by RT-qPCR, and the phosphorylation of CREB, which is the transcriptional factor controlling the expression of gluconeogenetic genes, was detected by western blot. BBR reduced blood glucose levels, improved insulin and glucose tolerance, and suppressed lactate- and glucagon-induced hepatic gluconeogenesis in ob/ob and STZ-induced diabetic mice. Importantly, BBR blunted glucagon-induced glucose production and gluconeogenic gene expression in hepatocytes, presumably through reducing cAMP, which resulted in the phosphorylation of CREB. By utilizing a cAMP analogue, adenylate cyclase (AC), to activate cAMP synthetase, and an inhibitor of the cAMP degradative enzyme, phosphodiesterase (PDE), we revealed that BBR accelerates intracellular cAMP degradation. BBR reduces the intracellular cAMP level by activating PDE, thus blocking activation of downstream CREB and eventually downregulating gluconeogenic genes to restrain hepatic glucose production.

scholarly journals Glucose Turnover and Hepatocyte Glucose Production of Starved and Toxaemic Pregnant Sheep

1983 ◽  
Vol 36 (3) ◽  
pp. 271 ◽  
Author(s):  
M E Wastney ◽  
JE Wolff ◽  
R Bickerstaffe
Keyword(s):  
Continuous Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Production Rates ◽  
Hepatic Gluconeogenesis ◽  
Pregnant Sheep ◽  
Hepatic Glucose ◽  
Pregnancy Toxaemia ◽  
Maternal Glucose

Ewes bearing twins were starved for 10 days during the last month of gestation to induce ovine pregnancy toxaemia (OPT). Glucose turnover was measl,lred by a primed continuous infusion of [U_ '4C]_ and [6-3HJglucose at the end of 10 days of starvation (non-susceptible), or earlier when ewes became recumbent with OPT (susceptible). All ewes were slaughtered at the end of the infusion and hepatocytes were prepared in order to measure glucose production from different substrates. Many of the ewes had dead foetuses when slaughtered. Glucose production rates by hepatocytes with the substrates propionate, lactate or alanine were significantly less from the susceptible ewes than were those from non-susceptible ewes. These low rates were not stimulated by incubation with glucagon (10-8 M), glutamine or glycerol. Rates of glucose turnover and of hepatic glucose production from all substrates were higher for ewes with dead than with live foetuses. The data support the hypothesis that pathogenesis of OPT is related to an impairment of hepatic gluconeogenesis, and further suggest that, in starved pregnant ewes, maternal glucose production may be restrained in the presence of a live foetus.

Antisense oligonucleotides targeted against glucocorticoid receptor reduce hepatic glucose production and ameliorate hyperglycemia in diabetic mice

Metabolism ◽  
2005 ◽  
Vol 54 (7) ◽  
pp. 848-855 ◽  
Author(s):  
Yin Liang ◽  
Melville C. Osborne ◽  
Brett P. Monia ◽  
Sanjay Bhanot ◽  
Lynnetta M. Watts ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Antisense Oligonucleotides ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Diabetic Mice ◽  
Hepatic Glucose

Selective antagonism of the hepatic glucocorticoid receptor reduces hepatic glucose production

Metabolism ◽  
2006 ◽  
Vol 55 (9) ◽  
pp. 1255-1262 ◽  
Author(s):  
Dale S. Edgerton ◽  
Peer B. Jacobson ◽  
Terry J. Opgenorth ◽  
Bradley Zinker ◽  
David Beno ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose
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