Effects of long-term pharmacological inhibition of CGRP signaling on bone and glucose metabolism

2020 ◽  
Author(s):  
P Köhli ◽  
J Appelt ◽  
D Jahn ◽  
E Otto ◽  
A Baranowsky ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pharmacological Inhibition

scholarly journals Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Mayarling Francisca Troncoso ◽  
Mario Pavez ◽  
Carlos Wilson ◽  
Daniel Lagos ◽  
Javier Duran ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cardiac Hypertrophy ◽  
Glucose Uptake ◽  
Male Rats ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Elevated Glucose ◽  
Amp Activated Protein Kinase ◽  
Cultured Cardiomyocytes

Abstract Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Long Term Predictors of Post-Partum Glucose Metabolism in Women with Gestational Diabetes Mellitus

2010 ◽  
Vol 118 (08) ◽  
pp. 485-489 ◽  
Author(s):  
G. Seghieri ◽  
F. Tesi ◽  
A. De Bellis ◽  
R. Anichini ◽  
G. Fabbri ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Post Partum

Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium

2021 ◽  
Author(s):  
Ying Zhao ◽  
Yan Shu ◽  
Ning Zhao ◽  
Zili Zhou ◽  
Xiong Jia ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Circadian Rhythm ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Sleep Deprivation ◽  
Rhesus Macaques ◽  
Intravenous Glucose ◽  
Increased Risk ◽  
The Impact

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.

scholarly journals ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Shuohui Dong ◽  
Shuo Liang ◽  
Zhiqiang Cheng ◽  
Xiang Zhang ◽  
Li Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Cell Models ◽  
Primary Tumors ◽  
Pharmacological Inhibition ◽  
Potential Biomarker

Abstract Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

scholarly journals Chronic Microvascular Complications in Prediabetic States—An Overview

2020 ◽  
Vol 9 (10) ◽  
pp. 3289
Author(s):  
Angelika Baranowska-Jurkun ◽  
Wojciech Matuszewski ◽  
Elżbieta Bandurska-Stankiewicz
Keyword(s):  
Risk Factor ◽  
Glucose Metabolism ◽  
Microvascular Complications ◽  
Current Data ◽  
Chronic Complications ◽  
Prediabetic State ◽  
Complications Of Diabetes ◽  
Glucose Levels ◽  
Abnormal Glucose Metabolism

A prediabetic state is a major risk factor for the development of diabetes, and, because of an identical pathophysiological background of both conditions, their prevalence increases parallelly and equally fast. Long-term hyperglycemia is the main cause inducing chronic complications of diabetes, yet the range of glucose levels at which they start has not been yet unequivocally determined. The current data show that chronic microvascular complications of diabetes can be observed in patients with abnormal glucose metabolism in whom glycaemia is higher than optimal but below diagnostic criteria for diabetes. Prediabetes is a heterogenous nosological unit in which particular types are differently characterized and show different correlations with particular kinds of complications. Analysis of the latest research results shows the need to continue studies in a larger population and can imply the need to verify the currently employed criteria of diagnosing diabetes and chronic complications of diabetes in people with prediabetes.

scholarly journals Long-term prognostic utility of low-density lipoprotein (LDL) triglyceride in real-world patients with coronary artery disease and diabetes or prediabetes

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing-Lu Jin ◽  
Hui-Wen Zhang ◽  
Ye-Xuan Cao ◽  
Hui-Hui Liu ◽  
Qi Hua ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Real World ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
C Statistic ◽  
Prognostic Utility ◽  
Artery Disease ◽  
Stable Cad

Abstract Background Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. Methods A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. Results During a median of 5.1 (interquartile range 3.9 to 5.9) years’ follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149–2.955), 1.828 (1.165–2.867), 2.212 (1.396–3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively. Conclusions In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.

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