Garcinol promotes hepatic gluconeogenesis by inhibiting P300/CBP-associated factor in late-pregnant sows

2020 ◽  
pp. 1-8
Author(s):  
Weilei Yao ◽  
Jun Xia ◽  
Tongxin Wang ◽  
Juan Li ◽  
Lu Huang ◽  
...  
Keyword(s):  
Basal Diet ◽  
Isolated Hepatocytes ◽  
Enzyme Expression ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Forkhead Box ◽  
Hepatic Glucose ◽  
Diet Control ◽  
Gluconeogenic Enzyme ◽  
Interfering Rna

Abstract Disorder of hepatic glucose metabolism is the characteristic of late-pregnant sows. The purpose of our study was to look into the mechanism of garcinol on the improvement of hepatic gluconeogenic enzyme in late-pregnant sows. Thirty second- and third-parity sows (Duroc × Yorkshire × Landrace, n 10/diet) were fed a basal diet (control) or that diet supplemented with 100 mg/kg (Low Gar) or 500 mg/kg (High Gar) garcinol from day 90 of gestation to the end of farrowing. The livers were processed to measure enzymatic activity. Hepatocytes from pregnant sows were transfected with P300/CBP-associating factor (PCAF) small interfering RNA (siRNA) or treated with garcinol. Dietary garcinol had no effect on average daily feed intake, body weight (BW), backfat and BW gain of late-pregnant sows. Garcinol promoted plasma glucose levels in pregnant sows and newborn piglets. Garcinol up-regulated hepatic gluconeogenic enzyme expression and decreased PCAF activity. Garcinol had no effect on the expression of PPAR-γ co-activator 1α (PGC-1α) and Forkhead box O1 (FOXO1) but significantly increased their activity and decreased their acetylation in late-pregnant sows. Transfection of PCAF siRNA to hepatocytes of pregnant sows increased PGC-1α and FOXO1 activities. Furthermore, in hepatocytes of pregnant sows, garcinol treatment also up-regulated the activities of PGC-1α and FOXO1 and inhibited the acetylation of PGC-1α and FOXO1. Garcinol improves hepatic gluconeogenic enzyme expression in late-pregnant sows, and this may be due to the mechanism of down-regulating the acetylation of PGC-1α and FOXO1 induced by PCAF in isolated hepatocytes.

scholarly journals Prostaglandins E2 and F2α increase fructose 2,6-bisphosphate levels in isolated hepatocytes

1991 ◽  
Vol 274 (1) ◽  
pp. 309-312 ◽  
Author(s):  
A M Gómez-Foix ◽  
J E Rodríguez-Gil ◽  
J J Guinovart ◽  
F Bosch
Keyword(s):  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Glycolytic Flux ◽  
Dependent Manner ◽  
Hepatic Glucose Metabolism ◽  
Prostaglandin F2 Alpha ◽  
Hepatic Glucose ◽  
Dose Dependent ◽  
Prostaglandins E2 And F2α ◽  
Stimulation Of

In hepatocytes isolated from fed rats, prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) increased, in a time- and dose-dependent manner, fructose 2,6-bisphosphate [Fru(2,6)P2] levels and stimulated the glycolytic flux. The rise in Fru(2,6)P2 was related to an increase in glucose 6-phosphate levels which resulted from the stimulation of glycogenolysis. In cells obtained from 24 h-starved rats, no effects of either PGE2 or PGF2 alpha could be observed. In addition, when the stimulation of glycogenolysis was abolished by incubation of fed-rat hepatocytes in a Ca2(+)-depleted medium, Fru(2,6)P2 levels did not increase. Furthermore, no effects of PGs on 6-phosphofructo-2-kinase activity could be observed. These results indicate that PGE2 and PGF2 alpha show similar actions to Ca2(+)-dependent hormones on hepatic glucose metabolism.

Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog

1997 ◽  
Vol 273 (4) ◽  
pp. E674-E681 ◽  
Author(s):  
Owen P. McGuinness ◽  
Vickie Shau ◽  
Eric M. Benson ◽  
Mike Lewis ◽  
Robert T. Snowden ◽  
...  
Keyword(s):  
Metabolic Response ◽  
Glucose Production ◽  
Stress Hormone ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Response To Stress ◽  
Arteriovenous Difference ◽  
Arterial Glucose

The role of epinephrine and norepinephrine in contributing to the alterations in hepatic glucose metabolism during a 70-h stress hormone infusion (SHI) was investigated in four groups of chronically catheterized (20-h-fasted) conscious dogs. SHI increased glucagon (∼5-fold), epinephrine (∼10-fold), norepinephrine (∼10-fold), and cortisol (∼6-fold) levels. Dogs received either all the hormones (SHI; n = 5), all the hormones except epinephrine (SHI−Epi; n = 6), or all the hormones except norepinephrine (SHI−NE; n = 6). In addition, six dogs received saline only (Sal). Glucose production (Ra) and gluconeogenesis were assessed after a 70-h hormone or saline infusion with the use of tracer ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference techniques. SHI increased glucose levels (108 ± 2 vs. 189 ± 10 mg/dl) and Ra(2.6 ± 0.2 vs. 4.1 ± 0.3 mg ⋅ kg−1⋅ min−1) compared with Sal. The absence of an increase in epinephrine markedly attenuated these changes (glucose and Rawere 140 ± 6 mg/dl and 2.7 ± 0.4 mg ⋅ kg−1⋅ min−1, respectively). Only 25% of the blunted rise in Racould be accounted for by an attenuation of the rise in net hepatic gluconeogenic precursor uptake (0.9 ± 0.1, 1.5 ± 0.1, and 1.1 ± 0.2 mg ⋅ kg−1⋅ min−1for Sal, SHI, and SHI−Epi, respectively). The absence of an increase in norepinephrine did not blunt the rise in arterial glucose levels, Ra, or net hepatic gluconeogenic precursor uptake (they rose to 195 ± 21 mg/dl, 3.7 ± 0.5 mg ⋅ kg−1⋅ min−1, and 1.7 ± 0.2 mg ⋅ kg−1⋅ min−1, respectively). In summary, during chronic SHI, the rise in epinephrine exerts potent stimulatory effects on glucose production principally by enhancing hepatic glycogenolysis, although the rise in circulating norepinephrine has minimal effects.

Impact of continuous and pulsatile insulin delivery on net hepatic glucose uptake

2005 ◽  
Vol 289 (2) ◽  
pp. E232-E240 ◽  
Author(s):  
Jaime M. Grubert ◽  
Margaret Lautz ◽  
D. Brooks Lacy ◽  
Mary C. Moore ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Hepatic Metabolism ◽  
Insulin Delivery ◽  
Experimental Period ◽  
Constant Infusion ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Arterial Plasma ◽  
Hepatic Glucose Uptake

The pancreas releases insulin in a pulsatile manner; however, studies assessing the liver’s response to insulin have used constant infusion rates. Our aims were to determine whether the secretion pattern of insulin [continuous (CON) vs. pulsatile] in the presence of hyperglycemia 1) influences net hepatic glucose uptake (NHGU) and 2) entrains NHGU. Chronically catheterized conscious dogs fasted for 42 h received infusions including peripheral somatostatin, portal insulin (0.25 mU·kg−1·min−1), peripheral glucagon (0.9 ng·kg−1·min−1), and peripheral glucose at a rate double the glucose load to the liver. After the basal period, insulin was infused for 210 min at either four times the basal rate (1 mU·kg−1·min−1) or an identical amount in pulses of 1 and 4 min duration, followed by intervals of 11 and 8 min (CON, 1/11, and 4/8, respectively) in which insulin was not infused. A variable peripheral glucose infusion containing [3H]glucose clamped glucose levels at twice the basal level (∼200 mg/dl) throughout each study. Hepatic metabolism was assessed by combining tracer and arteriovenous difference techniques. Arterial plasma insulin (μU/ml) either increased from basal levels of 6 ± 1 to a constant level of 22 ± 4 in CON or oscillated from 5 ± 1 to 416 ± 79 and from 6 ± 1 to 123 ± 43 in 1/11 and 4/8, respectively. NHGU (−0.8 ± 0.3, 0.4 ± 0.2, and −0.9 ± 0.4 mg·kg−1·min−1) and net hepatic fractional extraction of glucose (0.04 ± 0.01, 0.04 ± 0.01, and 0.05 ± 0.01 mg·kg−1·min−1) were similar during the experimental period. Spectral analysis was performed to assess whether a correlation existed between the insulin secretion pattern and NHGU. NHGU was not augmented by pulsatile insulin delivery, and there is no evidence of entrainment in hepatic glucose metabolism. Thus the loss of insulin pulsatility per se likely has little or no impact on the effectiveness of insulin in regulating liver glucose uptake.

Effect of growth hormone on hepatic glucose and insulin metabolism after oral glucose in conscious dogs

1994 ◽  
Vol 267 (3) ◽  
pp. E454-E460
Author(s):  
Y. Okuda ◽  
J. Pena ◽  
J. Chou ◽  
J. B. Field
Keyword(s):  
Growth Hormone ◽  
Portal Vein ◽  
Hepatic Uptake ◽  
Oral Glucose ◽  
Gh Treatment ◽  
Insulin Metabolism ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Before And After

This study examined the effect of growth hormone (GH) on hepatic glucose metabolism and on the fractional extraction of insulin and glucagon after oral glucose administration. GH treatment [canine GH (0.75 mg/day for 7 days)] significantly increased basal portal vein and hepatic artery flow (P < 0.01 compared with pre-GH treatment). After GH treatment and after oral glucose, glucose levels significantly exceeded those before GH at 100 and 120 min in arterial and portal vein plasma and 120 min in the hepatic vein. The net hepatic uptake of glucose was similar before and after GH treatment. The increment of net nonhepatic splanchnic insulin balance above basal was 131 +/- 31 mU.kg-1.3 h-1 before and 272 +/- 46 mU.kg-1.3 h-1 after GH treatment (P < 0.05). An increase in fractional hepatic extraction of insulin occurred before GH treatment and was significantly greater at 60 min. In summary, despite the increased insulin content after GH administration, there was no change in hepatic uptake of glucose, indicating that the liver was also the site of insulin resistance.

scholarly journals Fermented Rice Germ Extract Ameliorates Abnormal Glucose Metabolism via Antioxidant Activity in Type 2 Diabetes Mellitus Mice

2021 ◽  
Vol 11 (7) ◽  
pp. 3091
Author(s):  
Ye Ji Hyun ◽  
Ju Gyeong Kim ◽  
Sung Keun Jung ◽  
Ji Yeon Kim
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Ferulic Acid ◽  
Fasting Blood Glucose ◽  
Liver Weight ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Abnormal Glucose Metabolism ◽  
Hepatic Glucose

Rice germ is an abundant source of ferulic acid, which is known for its anti-oxidant activity. This study aimed to evaluate the regulatory effects of fermented rice germ extracts on hepatic glucose metabolism in C57BL/KsJ-db/db mice. Rice germ was fermented with Lactobacillus plantarum and extracted with 30% ethanol (RG_30E) or 50% ethanol (RG_50E). Mice were fed modified AIN-93 diets containing fermented rice germ extracts and ferulic acid for 8 weeks. RG_50E significantly reduced food intake as well as liver weight and RG_30E and RG_50E improved glucose homeostasis, as indicated by fasting blood glucose levels and glucose tolerance. Hepatic triglyceride and total cholesterol levels were significantly decreased in db/db mice fed RG_30E and RG_50E. The antioxidant capacity of RG_30E and RG_50E was confirmed by a decrease in malondialdehyde levels and an increase in hepatic superoxide dismutase activity. The expression of genes related to glycolysis and gluconeogenesis was significantly regulated by RG_30E and RG_50E. These results suggest that fermented rice germ extracts have the potential to regulate hypoglycemia and hepatic glucose metabolism in type 2 diabetes db/db mice.

Lack of effect of parathyroid hormone on hepatic glucose metabolism in the dog

Metabolism ◽  
1981 ◽  
Vol 30 (5) ◽  
pp. 469-475 ◽  
Author(s):  
S. Bevilacqua ◽  
E. Barrett ◽  
E. Ferrannini ◽  
R. Gusberg ◽  
A. Stewart ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Glucose Metabolism ◽  
Hepatic Glucose Metabolism ◽  
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.

scholarly journals Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

2017 ◽  
Vol 312 (4) ◽  
pp. R626-R636 ◽  
Author(s):  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Camilla L. Schwartz ◽  
Jakob G. Knudsen ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Prolonged Exercise ◽  
Hepatic Glycogen ◽  
Glucose Content ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Single Bout ◽  
Substrate Choice

The liver is essential in maintaining and regulating glucose homeostasis during prolonged exercise. IL-6 has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim of this study was to investigate the role of skeletal muscle IL-6 on hepatic glucose regulation and substrate choice during prolonged exercise. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice (age, 12–14 wk) and littermate lox/lox (Control) mice were either rested (Rest) or completed a single bout of exercise for 10, 60, or 120 min, and the liver was quickly obtained. Hepatic IL-6 mRNA was higher at 60 min of exercise, and hepatic signal transducer and activator of transcription 3 was higher at 120 min of exercise than at rest in both genotypes. Hepatic glycogen was higher in IL-6 MKO mice than control mice at rest, but decreased similarly during exercise in the two genotypes, and hepatic glucose content was lower in IL-6 MKO than control mice at 120 min of exercise. Hepatic phosphoenolpyruvate carboxykinase mRNA and protein increased in both genotypes at 120 min of exercise, whereas hepatic glucose 6 phosphatase protein remained unchanged. Furthermore, IL-6 MKO mice had higher hepatic pyruvate dehydrogenase (PDH)Ser232 and PDHSer300 phosphorylation than control mice at rest. In conclusion, hepatic gluconeogenic capacity in mice is increased during prolonged exercise independent of muscle IL-6. Furthermore, Skeletal muscle IL-6 influences hepatic substrate regulation at rest and hepatic glucose metabolism during prolonged exercise, seemingly independent of IL-6 signaling in the liver.

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