Transcription Factor HMG Box-Containing Protein 1 (HBP1) Regulates Glycemic Homeostasis Through Modulation of Gluconeogenesis

Abstract Objectives Glycemic dysregulation is one of the major metabolic disorders, which has long been a significant public health issue. The liver plays a pivotal role in the maintenance of blood glucose homeostasis. Previous studies indicate that upon refeeding a high carbohydrate diet, the expression of transcription factor HMG box-containing protein 1 (HBP1) was elevated in mice livers, suggesting a role of HBP1 in carbohydrate metabolism. Therefore, the objective of the current study was to understand the molecular mechanisms through which HBP1 regulates glucose generation in the liver. Methods Both in vivo HBP1 knockdown mice and in vitro HepG2 cell line were employed as the experimental models. Results First, we observed that overnight fasting led to increased PEPCK but decreased HBP1 expression in mice livers, and subsequent addition of insulin reversed the expression pattern. More importantly, HBP1 knockout (KO) mice displayed a significantly higher blood glucose level (173 mg/dL) than that of the controls (98 mg/dL). Also, HBP1 KO led to impaired OGTT (oral glucose tolerance test) and ITT (insulin tolerance test). These data suggest that HBP1 might have a role in the regulation of gluconeogenesis in the liver. To unveil the molecular mechanism by which HBP1 regulates glucose homeostasis, we examined its role in gluconeogenesis. Administration of gluconeogenic stimulators glucagon (100 nM) and cAMP (0.5 ng/mL) resulted in increased expression of Phosphoenolpyruvate carboxykinase (PEPCK; encoded by the PCK1 gene), a key enzyme in gluconeogenesis, but decreased HBP1 expression in HepG2 cells. Last, HBP1 siRNA-mediated mRNA disruption led to elevated PEPCK expression, whereas ectopic expression of HBP1 (pcDNA3-HBP1-Flag) significantly suppressed it. Conclusions In conclusion, our data indicate that HBP1 might negatively regulate glucose production and support HBP1 as a novel biological regulator of blood glucose homeostasis. Funding Sources This work was supported by the grant to MOST 108–2320-B-039–051-MY3 C-Y Huang.

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Blackthorn Flower Extract Impact on Glycaemic Homeostasis in Normoglycemic and Alloxan-Induced Hyperglycaemic C57BL/6 Mice

Food Technology and Biotechnology ◽

10.17113/ftb.59.03.21.7057 ◽

2021 ◽

Vol 59 (3) ◽

Author(s):

Irena Crnić ◽

Tajana Frančić ◽

Petar Dragičević ◽

Vedran Balta ◽

Verica Dragović-Uzelac ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Glucose Homeostasis ◽

Serum Insulin ◽

Sugar Content ◽

Tolerance Test ◽

Oral Glucose ◽

Mice Model ◽

Flower Extract ◽

Prunus Spinosa

Research background. The use of plants and their extracts in treatments of chronic diseases is widely known in traditional medicine. The aim of this study is to determine the effects of 10-day consumption of Prunus spinosa L. flower extract on blood glucose, glycaemic load, serum α-amlyase and serum insulin, in normoglycaemic and hypergycaemic (alloxan) mice model. Experimental approach. Normoglycemic and hyperglycemic (alloxan treated, 150 mg/kg body mass) C57BL/6 mice were treated daily, during 10 days, with Prunus spinosa L. flower extract by gavage. The sugar content within extract was determined by HPLC analysis. In mice, blood and serum blood glucose level and OGTT-test were determined by blood glucometer. Serum insulin was determined by ELISA assay and α-amlyase by colourimetric assay. Results and conclusions. The Prunus spinosa L. flower extract increased glucose in normoglycaemic mice by 30 % after 1st and 5th day and by 17 % after 10th day of consumption in normoglycaemic mice. It is a consequence of released sugars because sugar analysis revealed 59.8 mg/L monosaccharides, mainly fructose (55.7 mg/L) and glucose (24.3 mg/L) within the extract. On the opposite, the extract consumption, reduced serum blood glucose in alloxan-induced hyperglycaemic mice by 29 % after 10 days of treatment. Oral glucose tolerance test also confirmed that that in the hyperglycaemic group treated with Prunus spinosa L. flower extract glucose homeostasis was improved and showed decrease in blood glucose, since the blood glucose over the period of 120 min, glucose homeostasis is faster achieved after treatment with shows that in Prunus spinosa L. flower extract. Serum insulin increased by 49 % and serum alpha amylase by 46 % after 10 days of treatment with Prunus spinosa L. flower extract in hyperglycaemic group. Thus, it can be concluded that Prunus spinosa L. flower extract improved glucose tolerance, enhanced insulin secretion and lowered serum α-amylase activity. Novelty and scientific contribution. The results examined for the first time the potential of Prunus spinosa L. flower extract in hyperglycaemia management.

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Metformin Targets Foxo1 to Control Glucose Homeostasis

Biomolecules ◽

10.3390/biom11060873 ◽

2021 ◽

Vol 11 (6) ◽

pp. 873

Author(s):

Xiaoqin Guo ◽

Xiaopeng Li ◽

Wanbao Yang ◽

Wang Liao ◽

James Zheng Shen ◽

...

Keyword(s):

Transcription Factor ◽

Blood Glucose ◽

Signaling Pathway ◽

Glucose Homeostasis ◽

Molecular Mechanisms ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Suppressive Effect ◽

Dependent Manner ◽

Glucose Lowering Effect

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.

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Effects of Overexpression of Neurosecretory Protein GL-Precursor Gene on Glucose Homeostasis and Insulin Sensitivity in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22094681 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4681

Author(s):

Keisuke Fukumura ◽

Yuki Narimatsu ◽

Shogo Moriwaki ◽

Eiko Iwakoshi-Ukena ◽

Megumi Furumitsu ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Insulin Sensitivity ◽

Glucose Homeostasis ◽

Mass Gain ◽

Tolerance Test ◽

Oral Glucose ◽

Insulin Levels ◽

Glucose Levels ◽

Increase Food Intake

A high-fat diet (HFD) quickly induces obesity with insulin resistance and hyperglycemia. We previously reported that a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), stimulates feeding and fat accumulation in mice. However, the effects of NPGL on insulin sensitivity and glucose homeostasis remain unknown. Hence, we subjected NPGL-precursor gene (Npgl)-overexpressing mice to the oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) under normal chow (NC) and HFD conditions. Npgl overexpression promoted body mass gain and tended to increase food intake of NC-fed mice, whereas it had little effect on HFD-fed mice. The OGTT showed elevated blood glucose and insulin levels in Npgl-overexpressing NC-fed mice 15 min after glucose administration. Both the OGTT and IPITT demonstrated that Npgl overexpression decreased blood glucose levels in HFD-fed mice 60 min after glucose and insulin treatments. Notably, Npgl overexpression increased adipose tissue masses only in NC-fed mice, and it decreased blood glucose and insulin levels in HFD-fed mice at the experimental end point. It also increased the mRNA expression of galanin, one of the feeding and metabolic regulatory neuropeptides, in the hypothalamus of HFD-fed mice. Therefore, NPGL may alleviate HFD-induced hyperglycemia and insulin resistance in mice.

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THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

Acta Endocrinologica ◽

10.1530/acta.0.0700373 ◽

1972 ◽

Vol 70 (2) ◽

pp. 373-384 ◽

Cited By ~ 22

Author(s):

W. N. Spellacy ◽

W. C. Buhi ◽

S. A. Birk

Keyword(s):

Growth Hormone ◽

Blood Glucose ◽

Plasma Insulin ◽

Tolerance Test ◽

Metabolic Effects ◽

Oral Glucose ◽

Hormone Levels ◽

Glucose Levels ◽

Ethynodiol Diacetate ◽

Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

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Faculty Opinions recommendation of A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11712956.13049054 ◽

2011 ◽

Author(s):

Michael Schemann ◽

Gemma Mazzuoli-Weber

Keyword(s):

Blood Glucose ◽

Glucose Homeostasis ◽

Blood Glucose Homeostasis

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Antidiabetic Effect of Aqueous Corrigiola telephiifolia in Streptozotocin- Induced Diabetic Rats

The Natural Products Journal ◽

10.2174/2210315509666181231162513 ◽

2020 ◽

Vol 10 (1) ◽

pp. 61-68 ◽

Cited By ~ 1

Author(s):

Morad Hebi ◽

Mohamed Eddouks

Keyword(s):

Blood Glucose ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Diabetic Rats ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Phytochemical Screening ◽

Antidiabetic Effect ◽

Glucose Levels ◽

Blood Glucose Levels

Background: Corrigiola telephiifolia Pourr, is a perennial species, woody distributed throughout the north of Africa. This plant is used in traditional Mediterranean preparations and has many traditional uses especially treatment of diabetes. Aim/Methods: The current research was carried out to evaluate the antidiabetic effect of Aerial Parts of Aqueous Extract (APAE) of Corrigiola telephiifolia (C. telephiifolia) on both normal and streptozotocin (STZ)-induced diabetic rats treated at a dose of 5 mg/kg for fifteen days. Additionally, the histopathological changes in the liver, morphometric analysis, Oral Glucose Tolerance Test (OGTT) in normal rats and preliminary phytochemical screening for various components were realized. Results: Single oral administration of the APAE of C. telephiifolia (5mg/kg) showed no significant change in glycaemia of normal and STZ-induced diabetic rats. In contrast, repeated oral administration of C. telephiifolia reduced blood glucose levels from 4.11 ± 0.10 mmol/L to 3.16 ± 0.16 mmol/L (p<0.01) 15 days after administration in normal rats. Furthermore, blood glucose levels decreased from 17.84 ± 1.75mmol/L to 1.93 ± 0.33 mmol/L (p<0.0001) in STZ diabetic rats after fifteen days of treatment. According to the oral glucose tolerance test, C. telephiifolia (5 mg/kg) was shown to prevent significantly the increase in blood glucose levels in normal treated rats 30 min after glucose administration when compared to the control group. Also, the liver architecture of diabetic rats treated by C. telephiifolia was improved when compared with the liver architecture of untreated diabetic rats. Concerning the preliminary phytochemical screening of C. telephiifolia, several compounds have been found such as polyphenols, flavonoids, saponins, mucilage and terpenoids. Conclusion: The results show that the aqueous extract of C. telephiifolia possesses significant antihyperglycemic activity.

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Effects of Different Methods Used to Take Blood Samples on Blood Glucose Measurements

Clinical Nursing Research ◽

10.1177/10547738211024782 ◽

2021 ◽

pp. 105477382110247

Author(s):

Eda Ergin ◽

Ayten Zaybak

Keyword(s):

Blood Glucose ◽

Glucose Tolerance Test ◽

Venous Blood ◽

Tolerance Test ◽

Capillary Blood ◽

Oral Glucose ◽

Blood Samples ◽

Significant Difference ◽

Measurement Results ◽

Quasi Experimental

The purpose of this study is to compare whether or not there is a difference between venous and capillary blood samples in blood glucose measurements and investigate the effects of different aseptic methods used in skin cleaning before collecting blood samples on measurement results. This quasi-experimental study was conducted with 109 patients. The capillary first and second blood drop values taken from the patients after fasting and at 2 hours following 75 g oral glucose tolerance test (OGTT) and capillary and venous blood glucose values were compared. There was no significant difference between the median venous blood glucose value and the capillary second blood drop value taken after wiping the finger with alcohol. There was no significant difference between the first and second blood drop values of capillary blood glucose 2 hours after OGTT.

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