scholarly journals Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia

Redox Biology ◽  
2021 ◽  
Vol 38 ◽  
pp. 101815
Author(s):  
Qifei Wang ◽  
Pu Wang ◽  
Zelian Qin ◽  
Xin Yang ◽  
Bailin Pan ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cell Function ◽  
Altered Glucose ◽  
Keloid Fibroblasts

scholarly journals PI3K/AKT Pathway Promotes Keloid Fibroblasts Proliferation by Enhancing Glycolysis Under Hypoxia

2021 ◽  
Author(s):  
Qifei Wang ◽  
Xin Yang ◽  
Jianxun Ma ◽  
Xiang Xie ◽  
Yimou Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Cell Function ◽  
Feedback Mechanism ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Hypoxic Conditions ◽  
Altered Glucose ◽  
Positive Feedback Mechanism ◽  
Keloid Fibroblasts

Abstract Background Keloids are disfiguring fibro-proliferative disorders characterized by glucose metabolism reprogramming, namely elevated glycolysis and compromised oxidative phosphorylation. Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains unclear. Results Our findings revealed that when the PI3K/AKT pathway was inactivated with LY294002 under hypoxia, the protein expression of glycolytic enzymes GLUT1, HK2, PFKFB3, PGK1, ENO1, PKM2, and LDHA decreased under hypoxia, while the amount of mitochondria and mitochondrial membrane potential (MMP) increased, and mitochondrial ultrastructure in KFb remained unchanged. The key parameters of extracellular acidification rate (ECAR) markedly diminished, and those of oxygen consumption rate (OCR) significantly increased after inhibition of the PI3K/AKT pathway. When the PI3K/AKT pathway was suppressed, the levels of ROS and mitochondrial ROS were significantly increased. Meanwhile, cell proliferation, migration, and invasion were inhibited, and apoptosis was increased when the PI3K/AKT pathway was blocked. Additionally, cell proliferation was compromised when KFb were treated with both SC79 (an activator of the PI3K/AKT pathway) and 2-DG (an inhibitor of glycolysis), compared to the SC79 group. Moreover, a positive feedback mechanism was demonstrated in the PI3K/AKT pathway and HIF-1α. Conclusions Our data collectively demonstrated that the PI3K/AKT pathway promotes proliferation and inhibits apoptosis in KFb under hypoxia by regulating glycolysis, indicating that the PI3K/AKT signaling pathway could be a therapeutic target for keloids.

scholarly journals Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study

2021 ◽  
Vol 9 (1) ◽  
pp. e002208
Author(s):  
Marcus Hompesch ◽  
Jahoon Kang ◽  
OakPil Han ◽  
Michael E Trautmann ◽  
Christopher H Sorli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Phase Ib ◽  
Link Type ◽  
Drug Concentrations

IntroductionTo evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.Research design and methodsThis phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure.ResultsTreatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up.ConclusionsThe glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide.Trial registration numberNCT02059564.

Pancreatic beta-cell function and glucose metabolism in human segmental pancreas and kidney transplantation

1993 ◽  
Vol 264 (3) ◽  
pp. E441-E449 ◽  
Author(s):  
E. Christiansen ◽  
H. B. Andersen ◽  
K. Rasmussen ◽  
N. J. Christensen ◽  
K. Olgaard ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Kidney Transplant ◽  
Beta Cell Function ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Secretion Rate ◽  
C Peptide ◽  
Insulin Secretion Rate

beta-Cell function and glucose metabolism were studied in eight insulin-dependent diabetic recipients of combined segmental pancreas and kidney transplant with peripheral insulin delivery (Px), in eight nondiabetic kidney-transplant individuals (Kx), and in eight normal subjects (Ns) after three consecutive mixed meals. All subjects had normal fasting plasma glucose, but increased basal levels of C-peptide were demonstrated in the transplant groups (P < 0.05 relative to Ns). Postprandial hyperglycemia was increased 14% in Kx and 32% in Px (P < 0.05), whereas compared with Ns postprandial C-peptide levels were increased three- and twofold, respectively, in Kx and Px (P < 0.05). Compared with Ns basal insulin secretion rate (combined model) was increased 2-fold in Kx and 1.4-fold in Px (P < 0.05). Maximal insulin secretion rate was reduced 25% in Px compared with Kx (P < 0.05) but not different from that of Ns (P NS). Also, maximal insulin secretion rate occurred later in Px than in controls (Tmax: Px 50 min, Kx 30 min, and Ns 32 min; P < 0.05). The total integrated insulin secretion was increased 1.4-fold in Px compared with Ns (P < 0.05) but decreased 1.4-fold compared with Kx (P < 0.05). Fasting and postprandial proinsulin-to-C-peptide molar ratios were inappropriately increased in Px compared with Kx and Ns. Basal hepatic glucose production was increased 43% in Px and 33% in Kx compared with Ns (P < 0.05). Postprandial total systemic glucose appearance was similar in all three groups, whereas peripheral glucose disposal was 15% reduced in Px (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function

Cell Reports ◽  
2019 ◽  
Vol 27 (13) ◽  
pp. 3939-3955.e6 ◽  
Author(s):  
Nora Yucel ◽  
Yu Xin Wang ◽  
Thach Mai ◽  
Ermelinda Porpiglia ◽  
Peder J. Lund ◽  
...  
Keyword(s):  
Stem Cell ◽  
Glucose Metabolism ◽  
Histone Acetylation ◽  
Cell Function ◽  
Muscle Stem Cell

scholarly journals The Impact of Obesity on Tumor Glucose Uptake in Breast and Lung Cancer

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Brooks P Leitner ◽  
Rachel J Perry
Keyword(s):  
Lung Cancer ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Protective Effects ◽  
Clinical Prognosis ◽  
Computed Tomography Images ◽  
Positron Emission ◽  
Altered Glucose ◽  
Poor Outcomes ◽  
The Impact

Abstract Obesity confers an increased incidence and poorer clinical prognosis in more than 10 cancer types. Paradoxically, obesity may provide protection from poor outcomes in lung cancer. Mechanisms for the obesity-cancer links are not fully elucidated, with altered glucose metabolism being a promising candidate. Using 18F-fluorodeoxyglucose positron-emission-tomography/computed tomography images from The Cancer Imaging Archive, we explored the relationship between body mass index (BMI) and glucose metabolism in several cancers. In 188 patients (BMI mean [SD] = 27.7 [5.1], range = 17.4–49.3 kg/m2), higher BMI was associated with greater tumor glucose uptake in breast cancer (r = 0.36; P = .02) and with lower tumor glucose uptake in non-small cell lung cancer (r = -0.26; P = .048) using two-sided Pearson correlations. No relationship was observed in soft tissue sarcoma or squamous cell carcinoma. Harnessing the National Cancer Institute’s open-access database, we demonstrate altered tumor glucose metabolism as a potential mechanism for the detrimental and protective effects of obesity on breast and lung cancer, respectively.

Altered glucose metabolism in pregnancy

1967 ◽  
Vol 98 (5) ◽  
pp. 602-608 ◽  
Author(s):  
William K. Graves ◽  
Robert Neff ◽  
Peter Mark
Keyword(s):  
Glucose Metabolism ◽  
Altered Glucose ◽  
In Pregnancy

Fuel-mediated teratogenesis: biochemical effects of hypoglycemia during neurulation in mouse embryos in vitro

1989 ◽  
Vol 257 (2) ◽  
pp. E269-E276 ◽  
Author(s):  
E. S. Hunter ◽  
T. W. Sadler
Keyword(s):  
Nucleic Acid ◽  
Glucose Metabolism ◽  
Severe Hypoglycemia ◽  
Acid Synthesis ◽  
Mouse Embryos ◽  
Nucleic Acid Synthesis ◽  
Glycolytic Metabolism ◽  
Whole Embryo Culture ◽  
Altered Glucose

Hypoglycemia has been reported to induce congenital malformations and growth retardation in rodent embryos during the period of neural tube closure in vitro. However, the biochemical alterations responsible for the production of the dysmorphogenic effects have not been evaluated. Therefore, the rates of glucose metabolism by glycolysis, citric acid cycle, oxidative pentose phosphate pathway (PPP), and anabolic utilization were evaluated in mouse embryos and extraembryonic membranes using the whole embryo culture technique. Altered glucose metabolism by glycolysis and oxidative PPP, as well as altered anabolic synthesis, were produced by exposure to hypoglycemia. In embryos exposed to mild hypoglycemia (80 mg/dl) altered metabolism by the PPP and an associated effect on nucleic acid synthesis were in part responsible for the dysmorphogenic effects of this treatment. In contrast, severe hypoglycemia (40 mg/dl) appeared to have an immediate effect on glycolytic metabolism in addition to effects on the PPP and nucleic acid synthesis. Therefore, a multifactorial biochemical mechanism contributes to the induction of malformations by severe hypoglycemia in mouse embryos in vitro. Furthermore, the differential effects of moderate vs. severe hypoglycemia on glycolytic metabolism, and possibly energy production, may account for the differences in the severity of these treatments on embryonic growth and the incidence of malformations.

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