scholarly journals Role of Magnesium in the Regulation of Hepatic Glucose Homeostasis

10.5772/57564 ◽  
2014 ◽  
Author(s):  
Chesinta Voma ◽  
Andrea M.P. Romani
Keyword(s):  
Glucose Homeostasis ◽  
Hepatic Glucose

scholarly journals TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiologic states

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Simiao Xu ◽  
Yangyang Liu ◽  
Ruixiang Hu ◽  
Min Wang ◽  
Oliver Stöhr ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucocorticoid Receptor ◽  
Glucose Homeostasis ◽  
Mouse Liver ◽  
Blood Glucose Concentration ◽  
Glucose Production ◽  
Binding Motif ◽  
Gene Promoters ◽  
Hepatic Glucose

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiologic and pathologic states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR-transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiologic fasting and feeding.

scholarly journals POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Alexandre Caron ◽  
Heather M Dungan Lemko ◽  
Carlos M Castorena ◽  
Teppei Fujikawa ◽  
Syann Lee ◽  
...  
Keyword(s):  
Energy Balance ◽  
Glucose Homeostasis ◽  
Adrenergic Receptor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Genetic Manipulations ◽  
Leptin Receptors ◽  
Hepatic Glucose ◽  
Sympathetic Nervous

Leptin is critical for energy balance, glucose homeostasis, and for metabolic and neuroendocrine adaptations to starvation. A prevalent model predicts that leptin’s actions are mediated through pro-opiomelanocortin (POMC) neurons that express leptin receptors (LEPRs). However, previous studies have used prenatal genetic manipulations, which may be subject to developmental compensation. Here, we tested the direct contribution of POMC neurons expressing LEPRs in regulating energy balance, glucose homeostasis and leptin secretion during fasting using a spatiotemporally controlled Lepr expression mouse model. We report a dissociation between leptin’s effects on glucose homeostasis versus energy balance in POMC neurons. We show that these neurons are dispensable for regulating food intake, but are required for coordinating hepatic glucose production and for the fasting-induced fall in leptin levels, independent of changes in fat mass. We also identify a role for sympathetic nervous system regulation of the inhibitory adrenergic receptor (ADRA2A) in regulating leptin production. Collectively, our findings highlight a previously unrecognized role of POMC neurons in regulating leptin levels.

scholarly journals Glucagon regulates hepatic mitochondrial function and biogenesis through FOXO1

2019 ◽  
Vol 241 (3) ◽  
pp. 265-278
Author(s):  
Wanbao Yang ◽  
Hui Yan ◽  
Quan Pan ◽  
James Zheng Shen ◽  
Fenghua Zhou ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Mitochondrial Function ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Complex Iii ◽  
Dependent Manner ◽  
Hepatic Glucose ◽  
Patients With Diabetes ◽  
High Level

Glucagon promotes hepatic glucose production maintaining glucose homeostasis in the fasting state. Glucagon maintains at high level in both diabetic animals and human, contributing to hyperglycemia. Mitochondria, a major place for glucose oxidation, are dysfunctional in diabetic condition. However, whether hepatic mitochondrial function can be affected by glucagon remains unknown. Recently, we reported that FOXO1 is an important mediator in glucagon signaling in control of glucose homeostasis. In this study, we further assessed the role of FOXO1 in the action of glucagon in the regulation of hepatic mitochondrial function. We found that glucagon decreased the heme production in a FOXO1-dependent manner, suppressed heme-dependent complex III (UQCRC1) and complex IV (MT-CO1) and inhibited hepatic mitochondrial function. However, the suppression of mitochondrial function by glucagon was largely rescued by deleting the Foxo1 gene in hepatocytes. Glucagon tends to reduce hepatic mitochondrial biogenesis by attenuating the expression of NRF1, TFAM and MFN2, which is mediated by FOXO1. In db/db mice, we found that hepatic mitochondrial function was suppressed and expression levels of UQCRC1, MT-CO1, NRF1 and TFAM were downregulated in the liver. These findings suggest that hepatic mitochondrial function can be impaired when hyperglucagonemia occurs in the patients with diabetes mellitus, resulting in organ failure.

The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents

2014 ◽  
Vol 307 (10) ◽  
pp. E859-E871 ◽  
Author(s):  
Greg M. Kowalski ◽  
Clinton R. Bruce
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Rodent Models ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Underlying Causes

The incidence of insulin resistance and type 2 diabetes (T2D) is increasing at alarming rates. In the quest to understand the underlying causes of and to identify novel therapeutic targets to treat T2D, scientists have become increasingly reliant on the use of rodent models. Here, we provide a discussion on the regulation of rodent glucose metabolism, highlighting key differences and similarities that exist between rodents and humans. In addition, some of the issues and considerations associated with assessing glucose homeostasis and insulin action are outlined. We also discuss the role of the liver vs. skeletal muscle in regulating whole body glucose metabolism in rodents, emphasizing the importance of defective hepatic glucose metabolism in the development of impaired glucose tolerance, insulin resistance, and T2D.

Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis

2002 ◽  
Vol 282 (2) ◽  
pp. E419-E427 ◽  
Author(s):  
Christian Meyer ◽  
Jean M. Dostou ◽  
Stephen L. Welle ◽  
John E. Gerich
Keyword(s):  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Postprandial Glucose ◽  
Systemic Circulation ◽  
Postprandial Period ◽  
Glucose Release ◽  
Hepatic Glucose ◽  
The Difference ◽  
Hepatic Glucose Release

Recent studies indicate a role for the kidney in postabsorptive glucose homeostasis. The present studies were undertaken to evaluate the role of the kidney in postprandial glucose homeostasis and to compare its contribution to that of liver and skeletal muscle. Accordingly, we used the double isotope technique along with forearm and renal balance measurements to assess systemic, renal, and hepatic glucose release as well as glucose uptake by kidney, skeletal muscle, and splanchnic tissues in 10 normal volunteers after ingestion of 75 g of glucose. We found that, during the 4.5-h postprandial period, 22 ± 2 g (30 ± 3% of the ingested glucose) were initially extracted by splanchnic tissues. Of the remaining 53 ± 2 g that entered the systemic circulation, 19 ± 3 g were calculated to have been taken up by skeletal muscle and 7.5 ± 1.7 g by the kidney (26 ± 3 and 10 ± 2%, respectively, of the ingested glucose). Endogenous glucose release during the postprandial period (16 ± 2 g), calculated as the difference between overall systemic glucose appearance and the appearance of ingested glucose in the systemic circulation, was suppressed 61 ± 3%. Surprisingly, renal glucose release increased twofold (10.6 ± 2.5 g) and accounted for ∼60% of postprandial endogenous glucose release. Hepatic glucose release (6.7 ± 2.2 g), the difference between endogenous and renal glucose release, was suppressed 82 ± 6%. These results demonstrate a hitherto unappreciated contribution of the kidney to postprandial glucose homeostasis and indicate that postprandial suppression of hepatic glucose release is nearly twofold greater than had been calculated in previous studies (42 ± 4%), which had assumed that there was no renal glucose release. We postulate that increases in postprandial renal glucose release may play a role in facilitating efficient liver glycogen repletion by permitting substantial suppression of hepatic glucose release.

scholarly journals TAZ inhibits GR and coordinates hepatic glucose homeostasis in normal physiologic states

2020 ◽  
Author(s):  
Simiao Xu ◽  
Yangyang Liu ◽  
Ruixiang Hu ◽  
Min Wang ◽  
Oliver Stöhr ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Blood Glucose Concentration ◽  
Hippo Pathway ◽  
Glucose Production ◽  
Effector Proteins ◽  
Binding Motif ◽  
Gene Promoters ◽  
Hepatic Glucose ◽  
The Hippo Pathway

AbstractThe elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiologic and pathologic states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate distinct roles of the hippo pathway effector proteins yes-associated protein 1 (YAP) and TAZ in liver physiology: while deletion of hepatic YAP has little effect on glucose homeostasis, hepatic TAZ protein expression decreases upon fasting and coordinates gluconeogenesis in response to physiologic fasting and feeding.

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

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics

Diabetes ◽  
1987 ◽  
Vol 36 (3) ◽  
pp. 274-283 ◽  
Author(s):  
A. D. Baron ◽  
L. Schaeffer ◽  
P. Shragg ◽  
O. G. Kolterman
Keyword(s):  
Type Ii ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Type Ii Diabetics ◽  
Glucose Output
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