scholarly journals Dietary Pi deprivation in rats affects liver cAMP, glycogen, key steps of gluconeogenesis and glucose production

2000 ◽  
Vol 352 (1) ◽  
pp. 227-232 ◽  
Author(s):  
Wensheng XIE ◽  
T. Luong TRAN ◽  
Diane T. FINEGOOD ◽  
Gérald VAN DE WERVE
Keyword(s):  
Glucose Level ◽  
Glucose Intolerance ◽  
Plasma Glucose ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Control Diet ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Deficient Diet ◽  
Pi Deprivation ◽  
Deficient Group

We previously reported [Xie, Li, Méchin and van de Werve (1999) Biochem. J. 343, 393–396] that dietary phosphate deprivation for 2 days up-regulated both the catalytic subunit and the putative glucose-6-phosphate translocase of the rat liver microsomal glucose-6-phosphatase system, suggesting that increased hepatic glucose production might be responsible for the frequent clinical association of hypophosphataemia and glucose intolerance. We now show that liver cAMP was increased in rats fed with a diet deficient in Pi compared with rats fed with a control diet. Accordingly, in the Pi-deficient group pyruvate kinase was inactivated, the concentration of phosphoenolpyruvate was increased and fructose 2,6-bisphosphate concentration was decreased. Phosphoenolpyruvate carboxykinase activity was marginally increased and glucokinase activity was unchanged by Pi deprivation. The liver glycogen concentration decreased in the Pi-deficient group. In the fed state, plasma glucose concentration was increased and plasma Pi and insulin concentrations were substantially decreased in the Pi-deficient group. All of these changes, except decreased plasma Pi, were cancelled in the overnight fasted Pi-deficient group. In the fasted Pi-deficient group, immediately after a glucose bolus, the plasma glucose level was elevated and the inhibition of endogenous glucose production was decreased. However, this mild glucose intolerance was not sufficient to affect the rate of fall of the glucose level after the glucose bolus. Taken together, these changes are compatible with a stimulation of liver gluconeogenesis and glycogenolysis by the Pi-deficient diet and further indicate that the liver might contribute to impaired glucose homeostasis in Pi-deficient states.

scholarly journals Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroko Ikeda ◽  
Naomi Yonemochi ◽  
Risa Mikami ◽  
Manabu Abe ◽  
Meiko Kawamura ◽  
...  
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Receptor Agonist ◽  
Plasma Glucose Level ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Mrna Levels ◽  
Systemic Injection ◽  
Glucose Levels ◽  
Hepatic Glucose

AbstractRecent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D2 receptor knockout mice. I.c.v. injection of quinpirole and l-sulpiride each increased mRNA levels of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, which are the key enzymes for hepatic gluconeogenesis. Systemic injection of the β2 adrenoceptor antagonist ICI 118,551 inhibited hyperglycemia induced by l-sulpiride, but not by quinpirole. In contrast, hyperglycemia induced by quinpirole, but not by l-sulpiride, was inhibited by hepatic vagotomy. These results suggest that stimulation of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves.

Importance of basal glucagon in maintaining hepatic glucose production during a prolonged fast in conscious dogs

1992 ◽  
Vol 263 (3) ◽  
pp. E541-E549 ◽  
Author(s):  
G. K. Hendrick ◽  
D. H. Wasserman ◽  
R. T. Frizzell ◽  
P. E. Williams ◽  
D. B. Lacy ◽  
...  
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Plasma Glucose Level ◽  
Hepatic Glucose Production ◽  
Hormone Replacement ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Test Period ◽  
Conscious Dogs ◽  
Prolonged Fast

We undertook studies in conscious dogs to assess the role of basal glucagon in stimulating glucose production after a 7-day fast. Two protocols consisting of a 40-min basal period (-40 to 0 min), and a 180-min test period (0-180 min) were used. During the test period of the first protocol (hormone replacement; n = 4), somatostatin was infused (0.8 micrograms.kg-1.min-1) along with basal intraportal replacement amounts of insulin and glucagon, whereas in the second protocol (glucagon deficiency; n = 5), somatostatin plus insulin alone were infused. Glucose production and gluconeogenesis were measured using tracer and arteriovenous difference techniques. Plasma insulin levels were similar during the test period in both protocols (6 +/- 1 microU/ml). The plasma immunoreactive glucagon level in the control protocol averaged 50 +/- 8 pg/ml, whereas in the glucagon-deficiency protocol the level fell from 50 +/- 8 to 29 +/- 8 pg/ml (P less than 0.05). The plasma glucose level and the rate of glucose production were unchanged during bihormonal replacement. During glucagon deficiency the plasma glucose level was held constant at 100 +/- 4 mg/dl by glucose infusion. Tracer-determined endogenous glucose production fell from 1.8 +/- 0.1 to 1.0 +/- 0.1 mg.kg-1.min-1 by 30 min (P less than 0.05). After 3 h of glucagon deficiency, gluconeogenic conversion of alanine to glucagon was reduced 40% and the hepatic fractional extraction of alanine was reduced by 45%. The efficiency of the gluconeogenic process within the liver was not altered by glucagon deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

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

scholarly journals The impact of obesity, sex, and diet on hepatic glucose production in cats

2009 ◽  
Vol 296 (4) ◽  
pp. R936-R943 ◽  
Author(s):  
Saskia Kley ◽  
Margarethe Hoenig ◽  
John Glushka ◽  
Eunsook S. Jin ◽  
Shawn C. Burgess ◽  
...  
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Citrate Synthase ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Glucose Metabolism ◽  
Peripheral Insulin Resistance ◽  
Pyruvate Cycling ◽  
Hepatic Glucose ◽  
The Impact

Obesity is a risk factor for type 2 diabetes in cats. The risk of developing diabetes is severalfold greater for male cats than for females, even after having been neutered early in life. The purpose of this study was to investigate the role of different metabolic pathways in the regulation of endogenous glucose production (EGP) during the fasted state considering these risk factors. A triple tracer protocol using 2H2O, [U-13C3]propionate, and [3,4-13C2]glucose was applied in overnight-fasted cats (12 lean and 12 obese; equal sex distribution) fed three different diets. Compared with lean cats, obese cats had higher insulin ( P < 0.001) but similar blood glucose concentrations. EGP was lower in obese cats ( P < 0.001) due to lower glycogenolysis and gluconeogenesis (GNG; P < 0.03). Insulin, body mass index, and girth correlated negatively with EGP ( P < 0.003). Female obese cats had ∼1.5 times higher fluxes through phosphoenolpyruvate carboxykinase ( P < 0.02) and citrate synthase ( P < 0.05) than male obese cats. However, GNG was not higher because pyruvate cycling was increased 1.5-fold ( P < 0.03). These results support the notion that fasted obese cats have lower hepatic EGP compared with lean cats and are still capable of maintaining fasting euglycemia, despite the well-documented existence of peripheral insulin resistance in obese cats. Our data further suggest that sex-related differences exist in the regulation of hepatic glucose metabolism in obese cats, suggesting that pyruvate cycling acts as a controlling mechanism to modulate EGP. Increased pyruvate cycling could therefore be an important factor in modulating the diabetes risk in female cats.

Contribution of cortisol to glucose counterregulation in humans

1989 ◽  
Vol 257 (1) ◽  
pp. E35-E42 ◽  
Author(s):  
P. De Feo ◽  
G. Perriello ◽  
E. Torlone ◽  
M. M. Ventura ◽  
C. Fanelli ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects ◽  
Plasma Glucose Concentration ◽  
Cortisol Increase

To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Regulation of glucose turnover and hormonal responses during electrical cycling in tetraplegic humans

1996 ◽  
Vol 271 (1) ◽  
pp. R191-R199 ◽  
Author(s):  
M. Kjaer ◽  
S. F. Pollack ◽  
T. Mohr ◽  
H. Weiss ◽  
G. W. Gleim ◽  
...  
Keyword(s):  
Heart Rate ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hormonal Responses ◽  
Hepatic Glucose ◽  
Exercise Period ◽  
Exercise Activity ◽  
Beta Hydroxybutyrate

To examine the importance of blood-borne vs. neural mechanisms for hormonal responses and substrate mobilization during exercise, six spinal cord-injured tetraplegic (C5-T1) males (mean age: 35 yr, range: 24-55 yr) were recruited to perform involuntary, electrically induced cycling [functional electrical stimulation (FES)] to fatigue for 24.6 +/- 2.3 min (mean and SE), and heart rate rose from 67 +/- 7 (rest) to 107 +/- 5 (exercise) beats/min. Voluntary arm cranking in tetraplegics (ARM) and voluntary leg cycling in six matched, long-term immobilized (2-12 mo) males (Vol) served as control experiments. In FES, peripheral glucose uptake increased [12.4 +/- 1.1 (rest) to 19.5 +/- 4.3 (exercise) mumol.min-1.kg-1; P < 0.05], whereas hepatic glucose production did not change from basal values [12.4 +/- 1.4 (rest) vs. 13.0 +/- 3.4 (exercise) mumol.min-1.kg-1]. Accordingly, plasma glucose decreased [from 5.4 +/- 0.3 (rest) to 4.7 +/- 0.3 (exercise) mmol/l; P < 0.05]. Plasma glucose did not change in response to ARM or Vol. Plasma free fatty acids and beta-hydroxybutyrate decreased only in FES experiments (P < 0.05). During FES, increases in growth hormone (GH) and epinephrine and decreases in insulin concentrations were abolished. Although subnormal throughout the exercise period, norepinephrine concentrations increased during FES, and responses of heart rate, adrenocorticotropic hormone, beta-endorphin, renin, lactate, and potassium were marked. In conclusion, during exercise, activity in motor centers and afferent muscle nerves is important for normal responses of GH, catecholamines, insulin, glucose production, and lipolysis. Humoral feedback and spinal or simple autonomic nervous reflex mechanisms are not sufficient. However, such mechanisms are involved in redundant control of heart rate and neuroendocrine activity in exercise.

scholarly journals Control of gluconeogenic genes during intense/prolonged exercise: hormone-independent effect of muscle-derived IL-6 on hepatic tissue and PEPCK mRNA

2009 ◽  
Vol 107 (6) ◽  
pp. 1830-1839 ◽  
Author(s):  
Sébastien Banzet ◽  
Nathalie Koulmann ◽  
Nadine Simler ◽  
Hervé Sanchez ◽  
Rachel Chapot ◽  
...  
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Independent Effect ◽  
Hepatic Tissue ◽  
Hepatic Glycogen ◽  
Mrna Levels ◽  
Hepatic Glucose ◽  
Responsive Gene ◽  
Gene Mrna

Prolonged intense exercise is challenging for the liver to maintain plasma glucose levels. Hormonal changes cannot fully account for exercise-induced hepatic glucose production (HGP). Contracting skeletal muscles release interleukin-6 (IL-6), a cytokine able to increase endogenous glucose production during exercise. However, whether this is attributable to a direct effect of IL-6 on liver remains unknown. Here, we studied hepatic glycogen, gluconeogenic genes, and IL-6 signaling in response to one bout of exhaustive running exercise in rats. To determine whether IL-6 can modulate gluconeogenic gene mRNA independently of exercise, we injected resting rats with recombinant IL-6. Exhaustive exercise resulted in a profound decrease in liver glycogen and an increase in gluconeogenic gene mRNA levels, phosphoenolpyruvate-carboxykinase (PEPCK), glucose-6-phosphatase (G6P), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), suggesting a key role for gluconeogenesis in hepatic glucose production. This was associated to an active IL-6 signaling in liver tissue, as shown by signal transducer and activator of transcription and CAAT/enhancer binding protein-β phosphorylation and IL-6-responsive gene mRNA levels at the end of exercise. Recombinant IL-6 injection resulted in an increase in IL-6-responsive gene mRNA levels in the liver. We found a dose-dependent increase in PEPCK gene mRNA strongly correlated with IL-6-induced gene mRNA levels. No changes in G6P and PGC-1α mRNA levels were found. Taken together, our results suggest that, during very demanding exercise, muscle-derived IL-6 could help increase HGP by directly upregulating PEPCK mRNA abundance.

Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity

1993 ◽  
Vol 265 (2) ◽  
pp. E275-E283 ◽  
Author(s):  
M. Kjaer ◽  
K. Engfred ◽  
A. Fernandes ◽  
N. H. Secher ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Constant Infusion ◽  
Intense Exercise ◽  
Nerve Activity ◽  
Hepatic Glucose ◽  
Sympathoadrenergic Activity ◽  
Exercise In Humans

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

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