bims-glecem 2022-08-21 papers

Issue of 2022‒08‒21
seven papers selected by
Dipsikha Biswas, Københavns Universitet

Mol Nutr Food Res. 2022 Aug 16. e2200182

Calorie Restriction Enhanced Glycogen Metabolism to Compensate for Lipid Insufficiency.

Lili Hu, Xinyi Xia, Yue Zong, Yunjie Gu, Li Wei, Jun Yin.

SCOPE: This study aimed to investigate the metabolic phenotype and mechanism of 40% calorie restriction (CR) in mice.METHODS AND RESULTS: CR mice exhibited super-stable blood glucose, as evidenced by increased fasting blood glucose (FBG), decreased postprandial blood glucose, and reduced glucose fluctuations. Additionally, both fasting plasma insulin and the homeostasis model assessment of insulin resistance increased significantly in CR mice. Compared with control, the phosphorylation of insulin receptor substrates-1 and serine/threonine kinase decreased in liver and fat but increased in muscle of CR mice after insulin administration, indicating hepatic and adipose insulin resistance, and muscle insulin sensitization. CR reduced visceral fat much more than subcutaneous fat. The elevated FBG was negatively correlated with low-level fasting β-hydroxybutyrate, which may result from insufficient free fatty acids and diminished ketogenic ability in CR mice. Furthermore, liver glycogen increased dramatically in CR mice. Analysis of glycogen metabolism related proteins indicated active glycogen synthesis and decomposition. Additionally, CR elevated plasma corticosterone and hypothalamic orexigenic gene expression.
CONCLUSION: CR induced lipid insufficiency and stress, resulting in global physiological insulin resistance except muscle and enhanced glycogen metabolism, culminating in the stability of blood glucose manifested in increased FBG, which compensated for insufficient blood ketones. This article is protected by copyright. All rights reserved.

Keywords: GSK3β; HOMA-IR; hunger; ketogenesis; starvation

DOI: https://doi.org/10.1002/mnfr.202200182

Mol Cell. 2022 Aug 18. pii: S1097-2765(22)00712-2. [Epub ahead of print]82(16): 2918-2921

PYGBacking on glycogen metabolism to fuel early memory T cell recall responses.

Joseph Longo, McLane J Watson, Matthew J Vos, Kelsey S Williams, Russell G Jones.

Zhang et al. (2022) show that TCR signaling promotes the phosphorylation and activation of glycogen phosphorylase B (PYGB) in CD8+ memory T (Tmem) cells. PYGB-dependent glycogen mobilization provides a carbon source to support glycolysis and early Tmem cell recall responses.

DOI: https://doi.org/10.1016/j.molcel.2022.07.016

Arch Med Sci. 2022 ;18(4): 1095-1099

The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience.

Joanna Bidiuk, Zbigniew A Gaciong, Piotr Sobieraj.

Introduction: Recently published case reports suggest the benefit of empagliflozin use in subjects with glycogen storage disease Ib (GSD Ib).Methods: We present the clinical and laboratory data of 2 adult brothers with GSD Ib treated with empagliflozin for 12 months.
Results: There was no severe infection during administration of empagliflozin. The improvement of clinical symptoms of inflammatory bowel disease and arthritis along with reduction in serum CRP levels and urinary albumin excretion was noted. Neutrophil count increased, allowing for reduction or temporary withdrawal of G-CSF treatment.
Conclusions: Empagliflozin may be a new safe treatment in GSD Ib patients with an advanced stage of the disease.

Keywords: empagliflozin; glycogen storage disease type Ib; inflammatory diseases; neutrophil dysfunction

DOI: https://doi.org/10.5114/aoms/150029

Redox Biol. 2022 Aug 08. pii: S2213-2317(22)00192-6. [Epub ahead of print]56 102420

Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β.

Yingying Shu, Chaochun Zou, Yuqing Cai, Qiangqiang He, Xiaowei Wu, Haibin Zhu, Meiyu Qv, Yunqi Chao, Chengyun Xu, Lanfang Tang, Ximei Wu.

Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3β (GSK3β) at Cys14, which activated GSK3β and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3β in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3β and subsequent GSK3β activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.

Keywords: Cognitive disorder; GSK3β; Hypoglycemia; S-nitrosylation; VC

DOI: https://doi.org/10.1016/j.redox.2022.102420

Int J Radiat Biol. 2022 Aug 17. 1-15

Increased glucose influx and glycogenesis in lung cancer cells surviving after irradiation.

Avgi Tsolou, Dimitrios Koparanis, Ioannis Lamprou, Alexandra Giatromanolaki, Michael I Koukourakis.

PURPOSE: Lung cancer is considered as one of the most frequent malignancies worldwide. Radiotherapy is the main treatment modality applied for locally advanced disease, but remnant surviving cancer tissue results in disease progression in the majority of irradiated lung carcinomas. Metabolic reprogramming is regarded as a cancer hallmark and is associated with resistance to radiation therapy. Here, we explored metabolic alterations possibly related to cancer cell radioresistance.MATERIALS AND METHODS: We compared the expression of metabolism-related enzymes in the parental A549 lung cancer cell line along with two new cell lines derived from A549 cells after recovery from three (A549-IR3) and six (A549-IR6) irradiation doses with 4Gy. Differential GLUT1 and GYS1 expression on proliferation and radioresistance were also comparatively investigated.
RESULTS: A549-IR cells displayed increased extracellular glucose absorption, and enhanced mRNA and protein levels of the GLUT1 glucose transporter. GLUT1 inhibition with BAY-876, suppressed cell proliferation and the effect was significantly more profound on A549-IR3 cells. Protein levels of molecules associated with aerobic or anaerobic glycolysis, or the phosphate pentose pathway were similar in all three cell lines. However, Glycogen Synthase 1 (GYS1) was upregulated, especially in the A549-IR3 cell line, suggestive of glycogen accumulation in cells surviving post irradiation. GYS1-gene silencing repressed the proliferation capacity of A549, but this increased their radioresistance. The radio-protective effect of the suppression of proliferative activity induced by GYS1 silencing did not protect A549-IR3 cells against further irradiation.
CONCLUSIONS: These findings indicate that GYS1 activity is a critical component of the metabolism of lung cancer cells surviving after fractionated radiotherapy. Targeting the glycogen metabolic reprogramming after irradiation may be a valuable approach to pursue eradication of the post-radiotherapy remnant of disease.

Keywords: lung cancer; metabolic reprogramming; radioresistance; radiotherapy

DOI: https://doi.org/10.1080/09553002.2022.2113837

Med Sci Sports Exerc. 2022 Aug 12.

Extended Match Time Exacerbates Fatigue and Impacts Physiological Responses in Male Soccer Players.

Magni Mohr, Georgios Ermidis, Athanasios Z Jamustas, Jeppe Vigh-Larsen, Athanasios Poulios, Dimitrios Draganidis, Konstantinos Papanikolaou, Panagiotis Tsimeas, Dimitrios Batsilas, Georgios Loules, Alexios Batrakoulis, Apostolos Sovatzidis, Jakob L Nielsen, Theofanis Tzatzakis, Charikleia K Deli, Lars Nybo, Petur Krustrup, Ioannis G Fatouros.

PURPOSE: This study evaluated how extended match time (90 + 30 min) affected physiological responses and fatigue in male soccer players.METHODS: Twenty competitive players (age 21 ± 2 [±SD] years; VO2max 59 ± 4 ml/min/kg) completed an experimental match with their activity pattern and HR assessed throughout the game, while countermovement jump (CMJ) performance and repeated sprint ability (RSA) were tested and quadriceps muscle biopsies and venous blood samples taken at baseline and after 90 and 120 min of match-play.
RESULTS: Less high-intensity running (12%) was performed in extra time in association with fewer intense accelerations and decelerations per minute compared to normal time. Peak sprint speed was 11% lower in extra time compared to normal time, and fatigue also manifested in impaired post-match RSA and CMJ performance (all p < 0.05). Muscle glycogen declined from 373 ± 59 at baseline to 266 ± 64 mmol⸱kg-1 d.w. after 90 min, with a further decline to 186 ± 56 mmol⸱kg-1 d.w. following extra time (p < 0.05) and with single fiber analyses revealing depleted or very low glycogen levels in ~75% of both slow and fast twitch fibers. Blood glucose did not change during the first 90-min but declined (p < 0.05) to 81 ± 8 mg⸱dL after extra time. Plasma glycerol and ammonia peaked at 236 ± 33 mg⸱dL and 75 ± 21 μmol⸱L after the extra period.
CONCLUSIONS: These findings demonstrate exacerbated fatigue following extra time compared with normal time, which appears to be associated with muscle glycogen depletion, reductions in blood glucose levels and hyperammonemia. Together, this points to metabolic disturbances being a major part of the integrated and multifaceted fatigue response during extended soccer match-play.

DOI: https://doi.org/10.1249/MSS.0000000000003021