bims-glecem 2022-03-27 papers

bims-glecem

Biomed News

on Glycogen metabolism in exercise, cancer and energy metabolism

Issue of 2022‒03‒27
sixteen papers selected by
Dipsikha Biswas, Københavns Universitet

Hepatic glycogen participates in the regulation of hypothalamic pAkt/Akt ratio in high-sugar/high-fat diet-induced obesity.
Liver transplantation in glycogen storage disease: a single-center experience.
Effects of integrin-linked kinase on protein kinase b, glycogen synthase kinase-3β, and β-catenin molecules in ovarian cancer cells.
Dysregulation of miRNAs levels in GSK3β overexpressing mice and the role of miR-221-5p in synaptic function.
Synapto-protective effect of lithium on HIV-1 Tat-induced synapse loss in rat hippocampal cultures.
Yes-associated protein activation potentiates glycogen synthase kinase-3 inhibitor-induced proliferation of neonatal cardiomyocytes and iPS cell-derived cardiomyocytes.
Filament Negative Regulator CDC4 Suppresses Glycogen Phosphorylase Encoded GPH1 That Impacts the Cell Wall-Associated Features in Candida albicans.
Diagnostic accuracy of glycogen phosphorylase BB for myocardial infarction: A systematic review and meta-analysis.
Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report.
Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2: Evidence for Altered Myelination-Related Processes.
Ethylmalonyl-CoA pathway involved in polyhydroxyvalerate synthesis in Candidatus Contendobacter.
Investigation of the Repairing Effect and Mechanism of Oral Degraded Sericin on Liver Injury in Type II Diabetic Rats.
Whole body vibration remodels skeletal muscle via autophagy and energy metabolism in diabetic mice.
Inducible Systemic Gcn1 Deletion in Mice Leads to Transient Body Weight Loss upon Tamoxifen Treatment Associated with Decrease of Fat and Liver Glycogen Storage.
Glycogen hepatopathy in type-1 diabetes mellitus: A case report.
Dissecting Context-Specific Galectin Binding Using Glycoengineered Cell Libraries.

Metab Brain Dis. 2022 Mar 22.

Hepatic glycogen participates in the regulation of hypothalamic pAkt/Akt ratio in high-sugar/high-fat diet-induced obesity.

Breno P Casagrande, Allain A Bueno, Luciana P Pisani, Debora Estadella.

  The hypothalamus is a major integrating centre that controls energy homeostasis and plays a major role in hepatic glycogen (HGlyc) turnover. Not only do hypothalamic and hepatic Akt levels influence glucose homeostasis and glycogen synthesis, but exposure to high-sugar/high-fat diets (HSHF) can also lead to hypothalamic inflammation and HGlyc accumulation. HSHF withdrawal overall restores energy and glucose homeostasis, but the actual relationship between hypothalamic inflammation and HGlyc after short-term HSHF withdrawal has not yet been fully elucidated. Here we investigated the short-term effects of HSHF withdrawal preceded by a 30-day HSHF intake on the liver-hypothalamus crosstalk and glucose homeostasis. Sixty-day old male Wistar rats were fed for 30 days a control chow (n = 10) (Ct), or an HSHF diet (n = 20). On the 30th day of dietary intervention, a random HSHF subset (n = 10) had their diets switched to control chow for 48 h (Hw) whilst the remaining HSHF rats remained in the HSHF diet (n = 10) (Hd). All rats were anaesthetized and euthanized at the end of the protocol. We quantified HGlyc, Akt phosphorylation, inflammation and glucose homeostasis biomarkers. We also assessed the effect of propensity to obesity on those biomarkers, as detailed previously. Hd rats showed impaired glucose homeostasis, higher HGlyc and hypothalamic inflammation, and lower pAkt/Akt. Increased HGlyc was significantly associated with HSHF intake on pAkt/Akt lowered levels. We also found that HGlyc breakdown may have prevented a further pAkt/Akt drop after HSHF withdrawal. Propensity to obesity showed no apparent effect on hypothalamic inflammation or glucose homeostasis. Our findings suggest a comprehensive role of HGlyc as a structural and functional modulator of energy metabolism, and such roles may come into play relatively rapidly.

Keywords:  Hepatic glycogen; Hypothalamus; Liver; Obesogenic diet; Withdrawal

DOI:  https://doi.org/10.1007/s11011-022-00944-3
Orphanet J Rare Dis. 2022 Mar 21. 17(1): 127

Liver transplantation in glycogen storage disease: a single-center experience.

Zahra Beyzaei, Alireza Shamsaeefar, Kurosh Kazemi, Saman Nikeghbalian, Ali Bahador, Masoud Dehghani, Seyed-Ali Malekhosseini, Bita Geramizadeh.

  BACKGROUND: Glycogen storage diseases (GSDs) are inherited glycogen metabolic disorders which have various subtypes. GSDs of type I, III, IV, VI, and IX show liver involvement and are considered as hepatic types of GSDs. Thus, liver transplantation (LT) has been proposed as a final therapy for these types of GSD. LT corrects the primary hepatic enzyme defect; however, the long-term outcomes of LT in these patients have not been extensively evaluated so far. There are few reports in the English literature about the outcome of GSD patients after LT. There has been no report from Iran. The present retrospective study aimed to evaluate the long-term outcomes of eight patients with GSD types I, III, and IV who underwent LT in the affiliated hospitals of Shiraz University of Medical Sciences, from March 2013 to June 2021. During this period, there were no patients with GSD VI and IX identified in this center.RESULTS: The median time of diagnosis of the GSDs and at transplant was 1 year and 11 years, respectively. All eight transplanted patients were alive at the time of follow-up in this study. None of them required a re-transplant. All of the patients showed normalized liver enzymes after LT with no sign of hypoglycemia.
CONCLUSIONS: LT is an achievable treatment for end-stage hepatic involvement of GSDs with a cure for metabolic deficiency. Our experience in these eight patients shows a favorable outcome with no mortality and no major complication.

Keywords:  Cirrhosis; Glycogen storage disease; Liver transplantation; Metabolic control; Outcome

DOI:  https://doi.org/10.1186/s13023-022-02284-y
Iran J Basic Med Sci. 2021 Nov;24(11): 1500-1508

Effects of integrin-linked kinase on protein kinase b, glycogen synthase kinase-3β, and β-catenin molecules in ovarian cancer cells.

Seda Mehtap Sarı Kılıçaslan, Zerrin İncesu.

  Objectives: This study examines the impact of integrin-linked kinase (ILK), protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β), and β-catenin signal molecules in SKOV-3 ovarian cancer cells adhered to fibronectin.Materials and Methods: Expression levels of α4, αv, β1, and β6 integrin subunits known as the fibronectin ligand were investigated with the flow cytometry technique. The effects of ILK, AKT, GSK-3β, and β-catenin on the binding of SKOV-3 cells to fibronectin were examined by using the Real-Time Cellular Analysis (RTCA) method. Additionally, the interaction of these proteins was investigated by using Western blot analysis.
Results: The results show that the expression levels of integrin subunits were ranked as αv (67.8%), followed by α4 (48.55%), β6 (32.05%), and β1 (31%) on SKOV-3 cells. RTCA results showed that ILK (10 µM Cpd22), GSK-3β (50 μM GSK-3β inhibitor-XI), AKT (35 µM FPA 124), and β-catenin (50 μM cardamonin) inhibitors decreased significantly (P<0.01) binding to fibronectin at 24 hr. Western studies in SKOV-3 cells adhered to fibronectin have shown that in inhibition of ILK, AKT expression was strongly inhibited, whereas, in the inhibition of AKT, ILK expression was strongly inhibited. Furthermore, the expression of β-catenin is partially reduced in inhibition of these two molecules. In β-catenin inhibition, AKT and ILK expressions are also strongly inhibited.
Conclusion: ILK, AKT, GSK-3β, and β-catenin were found to be fundamental molecules in binding of SKOV-3 cells to fibronectin. ILK and AKT affect strongly the level of expression of each other, and both also affect the signal path of β-catenin.

Keywords:  Beta-catenin; Epithelial ovarian cancer; Fibronectin; GSK-3beta; Integrin

DOI:  https://doi.org/10.22038/IJBMS.2021.58716.13042
Neuroscience. 2022 Mar 21. pii: S0306-4522(22)00147-6. [Epub ahead of print]

Dysregulation of miRNAs levels in GSK3β overexpressing mice and the role of miR-221-5p in synaptic function.

Ewa Banach, Aleksandra Szczepankiewicz, Leszek Kaczmarek, Tomasz Jaworski, Joanna Urban-Ciećko.

  Glycogen Synthase Kinase-3β (GSK-3β) is a highly expressed kinase in the brain, where it has an important role in synaptic plasticity. Aberrant activity of GSK-3β leads to synaptic dysfunction which results in the development of several neuropsychiatric and neurological diseases. Notably, overexpression of constitutively active form of GSK-3β (GSK-3β[S9A]) in mice recapitulates the cognitive and structural defects characteristic for neurological and psychiatric disorders. However, the mechanisms by which GSK-3β regulates synaptic functions are not clearly known. Here, we investigate the effects of GSK-3β overactivity on neuronal miRNA expression in the mouse hippocampus. We found that GSK-3β overactivity downregulates miRNA network with a potent effect on miR-221-5p (miR-221*). Next, characterization of miR-221* function in primary hippocampal cell culture transfected by miR-221* inhibitor, showed no structural changes in dendritic spine shape and density. Using electrophysiological methods, we found that downregulation of miR-221* increases excitatory synaptic transmission in hippocampal neurons, probably via postsynaptic mechanisms. Thus, our data reveal potential mechanism by which GSK-3β and miRNAs might regulate synaptic function and therefore also synaptic plasticity.

Keywords:  Electrophysiology; GSK-3β; Next Generation Sequencing; miRNA

DOI:  https://doi.org/10.1016/j.neuroscience.2022.03.024
Anim Cells Syst (Seoul). 2022 ;26(1): 1-9

Synapto-protective effect of lithium on HIV-1 Tat-induced synapse loss in rat hippocampal cultures.

Namgue Hong, Jeong-Soo Park, Hee Jung Kim.

  Human immunodeficiency virus type I (HIV-1) infection of the CNS produces synapse loss which correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). Lithium is mood stabilizer of unknown mechanism used to treat bipolar disorder and is known to exhibit neuroprotective properties. Here, we studied the effects of lithium on HIV-1 Tat-induced synapses between rat hippocampal neurons. The number of synapses was quantified to detect clusters of the scaffold protein postsynaptic density 95 (PSD95) which is clustered at glutamatergic synapses on cultured rat hippocampal neurons in vitro. Lithium protected synapses from HIV-1 Tat-induced synapse loss and subsequent neuronal death. This synaptic protection was prevented by both the activation of NMDA receptor leading to intracellular signaling and the regulatory pathway of lithium including inositol depletion and glycogen synthase kinase-3β (GSK-3β). These results suggest that mood stabilizers might be effective drugs to treat neurodegenerative disorders including HAND.

Keywords:  HIV-1 Tat; Lithium; PSD95; neuronal cell death; synapse loss

DOI:  https://doi.org/10.1080/19768354.2021.2018044
J Cell Physiol. 2022 Mar 21.

Yes-associated protein activation potentiates glycogen synthase kinase-3 inhibitor-induced proliferation of neonatal cardiomyocytes and iPS cell-derived cardiomyocytes.

Yusuke Kametani, Shota Tanaka, Yuriko Wada, Shota Suzuki, Ayaka Umeda, Kosuke Nishinaka, Yoshiaki Okada, Makiko Maeda, Shigeru Miyagawa, Yoshiki Sawa, Masanori Obana, Yasushi Fujio.

  Because mammalian cardiomyocytes largely cease to proliferate immediately after birth, the regenerative activity of the heart is limited. To date, much effort has been made to clarify the regulatory mechanism of cardiomyocyte proliferation because the amplification of cardiomyocytes could be a promising strategy for heart regenerative therapy. Recently, it was reported that the inhibition of glycogen synthase kinase (GSK)-3 promotes the proliferation of neonatal rat cardiomyocytes (NRCMs) and human iPS cell-derived cardiomyocytes (hiPSC-CMs). Additionally, Yes-associated protein (YAP) induces cardiomyocyte proliferation. The purpose of this study was to address the importance of YAP activity in cardiomyocyte proliferation induced by GSK-3 inhibitors (GSK-3Is) to develop a novel strategy for cardiomyocyte amplification. Immunofluorescent microscopic analysis using an anti-Ki-67 antibody demonstrated that the treatment of NRCMs with GSK-3Is, such as BIO and CHIR99021, increased the ratio of proliferative cardiomyocytes. YAP was localized in the nuclei of more than 95% of cardiomyocytes, either in the presence or absence of GSK-3Is, indicating that YAP was endogenously activated. GSK-3Is increased the expression of β-catenin and promoted its translocation into the nucleus without influencing YAP activity. The knockdown of YAP using siRNA or pharmacological inhibition of YAP using verteporfin or CIL56 dramatically reduced GSK-3I-induced cardiomyocyte proliferation without suppressing β-catenin activation. Interestingly, the inhibition of GSK-3 also induced the proliferation of hiPSC-CMs under sparse culture conditions, where YAP was constitutively activated. In contrast, under dense culture conditions, in which YAP activity was suppressed, the proliferative effects of GSK-3Is on hiPSC-CMs were not detected. Importantly, the activation of YAP by the knockdown of α-catenin restored the proproliferative activity of GSK-3Is. Collectively, YAP activation potentiates the GSK-3I-induced proliferation of cardiomyocytes. The blockade of GSK-3 in combination with YAP activation resulted in remarkable amplification of cardiomyocytes.

Keywords:  cardiomyocyte; catenins; cell proliferation; regeneration; signal transduction

DOI:  https://doi.org/10.1002/jcp.30724
J Fungi (Basel). 2022 Feb 26. pii: 233. [Epub ahead of print]8(3):

Filament Negative Regulator CDC4 Suppresses Glycogen Phosphorylase Encoded GPH1 That Impacts the Cell Wall-Associated Features in Candida albicans.

Wei-Chung Lai, Hsiao-Chi Hsu, Chun-Wen Cheng, Shao-Hung Wang, Wan Chen Li, Po-Szu Hsieh, Tzu-Ling Tseng, Ting-Hui Lin, Jia-Ching Shieh.

  We have previously identified Candida albicans GPH1 (orf19.7021) whose protein product was associated with C. albicans Cdc4. The GPH1 gene is a putative glycogen phosphorylase because its Saccharomyces cerevisiae homolog participates in glycogen catabolism, which involves the synthesis of β-glucan of the fungal cell wall. We made a strain whose CaCDC4 expression is repressed, and GPH1 is constitutively expressed. We established a GPH1 null mutant strain and used it to conduct the in vitro virulence assays that detect cell wall function. The in vitro virulence assay is centered on biofilm formation in which analytic procedures are implemented to evaluate cell surface hydrophobicity; competence, either in stress resistance, germ tube formation, or fibronection association; and the XTT-based adhesion and biofilm formation. We showed that the constitutively expressed GPH1 partially suppresses filamentation when the CaCDC4 expression is repressed. The C. albicans Gph1 protein is reduced in the presence of CaCdc4 in comparison with the absence of CaCdc4. Compared with the wild-type strain, the gph1Δ/gph1Δ mutant displayed a reduction in the capability to form germ tubes and the cell surface hydrophobicity but an increase in binding with fibronectin. Compared with the wild-type strain, the gph1Δ/gph1Δ mutant showed a rise in adhesion, the initial stage of biofilm formation, but displayed a similar capacity to form a mature biofilm. There was no major impact on the gph1Δ/gph1Δ mutant regarding the conditions of cell wall damaging and TOR pathway-associated nutrient depletion. We conclude that GPH1, adversely regulated by the filament suppressor CDC4, contributes to cell wall function in C. albicans.

Keywords:  CaCDC4; Candida albicans; GPH1; cell wall; morphogenesis

DOI:  https://doi.org/10.3390/jof8030233
J Clin Lab Anal. 2022 Mar 24. e24368

Diagnostic accuracy of glycogen phosphorylase BB for myocardial infarction: A systematic review and meta-analysis.

Anup Ghimire, Subarna Giri, Niharika Khanal, Shivani Rayamajhi, Anjila Thapa, Anil Bist, Surya Devkota.

  PURPOSE: We tried to investigate the diagnostic accuracy of glycogen phosphorylase BB as a cardiac marker for myocardial infarction.METHODS: We searched through different electronic databases (PubMed, Google-scholar, Embase, and Cochrane Library) to locate relevant articles. Studies, with sufficient data to reconstruct a 2 × 2 contingency table, met our inclusion criteria were included. Three reviewers independently screened the articles. Discrepancies were resolved by other reviewers. Unpublished data were requested from the authors of the study via email. Subsequently, data extraction was done using a standardized form and quality assessment of studies using the QUADAS-2 tool. Meta-analysis was done using a bivariate model using R software.
RESULTS: Fourteen studies were selected for the final evaluation, which yielded the summary points: pooled sensitivity 87.77% (77.52%-93.72%, I2 = 86%), pooled specificity 88.45% (75.59%-94.99%, I2 = 88%), pooled DOR 49.37(14.53-167.72, I2 = 89%), and AUC of SROC was 0.923. The lambda value of the HSROC curve was 3.670. The Fagan plot showed that GPBB increases the pretest probability of myocardial infarction from 46% to 81% when positive, and it lowers the same probability to 12% when negative.
CONCLUSION: With these results, we can conclude that GPBB has modest accuracy in screening myocardial infarction, but the limitations of the study warrant further high-quality studies to confirm its usefulness in predicting myocardial infarction (MI).

Keywords:  cardiac biomarker; diagnosis; glycogen phosphorylase BB; myocardial infarction

DOI:  https://doi.org/10.1002/jcla.24368
J Med Case Rep. 2022 Mar 24. 16(1): 117

Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report.

Marit Lunde Dalen, Natalya Filipchuk Vigerust, Clara Hammarström, Henrik Holmstrøm, Jannicke Hanne Andresen.

  BACKGROUND: We report a case of the neonatal interstitial lung disease pulmonary interstitial glycogenosis in a girl with Jacobsen syndrome. While Jacobsen syndrome is caused by a deletion on the long arm of chromosome 11 and is genetically confirmed, pulmonary interstitial glycogenosis is of unknown etiology and is diagnosed by lung biopsy. Pulmonary interstitial glycogenosis has not previously been described in association with Jacobsen syndrome.CASE PRESENTATION: A term newborn small for gestational age Caucasian girl presented with respiratory distress, pulmonary hypertension, congenital heart defects, immunodeficiency, and thrombocytopenia. She was diagnosed with Jacobsen syndrome, but also had pulmonary interstitial glycogenosis, which contributed to significant morbidity. There was striking clinical improvement after steroid treatment of the pulmonary interstitial glycogenosis.
CONCLUSIONS: Interstitial lung disease should be considered as a differential diagnosis when respiratory distress and hypoxemia in the perinatal period worsens or persists despite standard treatment. Importantly, pulmonary interstitial glycogenosis may be treatable with corticosteroids. Whether there is a genetic link between pulmonary interstitial glycogenosis and Jacobsen syndrome is still unknown.

Keywords:  Case report; Immunodeficiency; Interstitial lung disease; Jacobsen syndrome; Neonate; Pulmonary hypertension; Thrombocytopenia

DOI:  https://doi.org/10.1186/s13256-022-03351-5
Cells. 2022 Mar 18. pii: 1036. [Epub ahead of print]11(6):

Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2: Evidence for Altered Myelination-Related Processes.

Evgeniy Svirin, Ekaterina Veniaminova, João Pedro Costa-Nunes, Anna Gorlova, Aleksei Umriukhin, Allan V Kalueff, Andrey Proshin, Daniel C Anthony, Andrey Nedorubov, Anna Chung Kwan Tse, Susanne Walitza, Lee Wei Lim, Klaus-Peter Lesch, Tatyana Strekalova.

  The interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (Tph2-/-) mice. In heterozygous male mice (Tph2+/-), there is a moderate reduction in brain 5-HT levels, and when they are exposed to stress, they exhibit increased aggression. Here, we exposed female Tph2+/- mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. Tph2+/- females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors Htr1a and Htr2a, glycogen synthase kinase-3 β (GSK-3β), and c-fos as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (Mbp), proteolipid protein 1 (Plp1), myelin-associated glycoprotein (Mag), and myelin oligodendrocyte glycoprotein (Mog). The expression of the plasticity markers synaptophysin (Syp) and cAMP response element binding protein (Creb), but not AMPA receptor subunit A2 (GluA2), were affected by genotype. Moreover, in a separate experiment, naïve female Tph2+/- mice showed signs of enhanced stress resilience in the modified swim test with repeated swimming sessions. Taken together, the combination of a moderate reduction in brain 5-HT with environmental challenges results in behavioral changes in female mice that resemble the aggression-related behavior and resilience seen in stressed male mutants; additionally, the combination is comparable to the phenotype of null mutants lacking neuronal 5-HT. Changes in myelination-associated processes are suspected to underpin the molecular mechanisms leading to aggressive behavior.

Keywords:  5-HT receptors; female aggression; glycogen synthase kinase-3 β (GSK-3β); myelination; predation stress; tryptophan hydroxylase-2 (Tph2)

DOI:  https://doi.org/10.3390/cells11061036
AMB Express. 2022 Mar 25. 12(1): 39

Ethylmalonyl-CoA pathway involved in polyhydroxyvalerate synthesis in Candidatus Contendobacter.

Chen Zhao, Chunchun Zhang, Zhiqiang Shen, Yanping Yang, Zhigang Qiu, Chenyu Li, Bin Xue, Xi Zhang, Xiaobo Yang, Shang Wang, Jingfeng Wang.

  Here a stable glycogen accumulating organisms (GAOs) system was operated by anaerobic-aerobic mode in the sequencing batch reactor. We focused on the metabolic mechanisms of PHAs storage from GAOs. Our system showed the classic characteristic of glycogen accumulating metabolism (GAM). Glycogen consumption was followed by acetic acid uptake to synthesize poly-β-hydroxyalkanoates (PHAs) during the anaerobic period, and glycogen was synthesized by PHAs degradation in the aerobic stage. Microbial community structure indicated that Candidatus Contendobacter was the most prevalent GAOs. We found that the ethylmalonyl-CoA (EMC) pathway was the crucial pathway supplying the core substance propionyl-CoA for poly-β-hydroxyvalerate (PHV) synthesis in Candidatus Contendobacter. All genes in EMC pathway were mainly located in Candidatus Contendobacter by gene source analysis. The key genes expression of EMC pathway increased with Candidatus Contendobacter enrichment, further validating that propionyl-CoA was synthesized by Candidatus Contendobacter predominantly via EMC pathway. Our work revealed the novel mechanisms underlying PHV synthesis through EMC pathway and further improved the intercellular storage metabolism of GAOs.

Keywords:  EMC pathway; Glycogen-accumulating organism; PHV; Propionyl-CoA

DOI:  https://doi.org/10.1186/s13568-022-01380-3
Biomolecules. 2022 Mar 13. pii: 444. [Epub ahead of print]12(3):

Investigation of the Repairing Effect and Mechanism of Oral Degraded Sericin on Liver Injury in Type II Diabetic Rats.

Zhen-Zhen Wei, Yu-Jie Weng, Yu-Qing Zhang.

  In the sericulture and silk production industry, sericin is discharged in the degumming wastewater, resulting in a large amount of wasted natural protein and environmental pollution. This study investigated the effect of degraded sericin recovered by the Ca(OH)2-ultrasound degumming method (a green process) on liver injury in T2D rats. After 4 weeks of dietary sericin supplementation, the liver masses and organ coefficients of the T2D rats improved compared with those of the model rats that were not fed sericin. Oral sericin activated the damaged PI3K/AKT/AMPK pathway to enhance glycogen synthesis, accelerate glycolysis, and inhibit gluconeogenesis. The protein expression levels of the inflammatory factors NF-κB, IL-6, and TNF-α in the T2D model group were up to two times higher than in the normal group. However, all three T2D groups that received oral sericin showed significant decreases in these factors to the level found in the normal group, indicating that inflammation in the body was significantly reduced. These results show that the sericin protein might improve glycogen synthesis, accelerate glycolysis, and inhibit gluconeogenesis by enhancing the anti-oxidation capability and reducing inflammatory reactions. Therefore, sericin recovered by Ca(OH)2 degradation has potential use in the development of functional health foods that can lower blood sugar.

Keywords:  inflammatory factors; oral administration; protein expression; sericin; signaling pathway

DOI:  https://doi.org/10.3390/biom12030444
Mol Med Rep. 2022 May;pii: 182. [Epub ahead of print]25(5):

Whole body vibration remodels skeletal muscle via autophagy and energy metabolism in diabetic mice.

Shanshan An, Dahao Wang, Xue Ma, Chang Liu.

  Hyperglycemia occurs due to a defect in insulin secretion or impaired biological functions, or both. The long‑term hyperglycemia during diabetes causes chronic damage and dysfunction of various tissues. Whole body vibration (WBV) has significant effects on lipid and glucose metabolism and endocrine and motor systems. In order to explore the effects of WBV on skeletal muscle, mice trained for 12 weeks with WBV (15 Hz, 30 min) were used as experimental subjects and their skeletal muscle morphology under the pathological state of diabetes was observed. In addition, the blood lipids, blood glucose, gastrocnemius muscle glycogen and mRNA and protein levels of autophagy and glucose metabolism biomarkers were compared among the three groups of mice via western blot and RT‑qPCR. The results showed that WBV can significantly reshape skeletal muscle morphology and upregulate high density lipoprotein. The expression of glucose‑6‑phosphatase (G6P), Beclin1 and Atg7 in the gastrocnemius muscle of the WBV group was significantly increased. Therefore, it can be concluded that WBV promotes skeletal muscle remodeling in diabetic mice. The present study confirmed that WBV can attenuate the development of diabetes melitus (DM) and lead to lower level low density lipoprotein in the blood. In addition, G6P level plays an important role in WBV‑treated DM model and may be used to monitor the effect of WBV in patients. The findings of the present study may provide a new molecular basis for WBV to play a therapeutic role in the treatment of diabetes and may have potential clinical applications in the future.

Keywords:  autophagy; diabetes; energy metabolism; whole body vibration

DOI:  https://doi.org/10.3892/mmr.2022.12698
Int J Mol Sci. 2022 Mar 16. pii: 3201. [Epub ahead of print]23(6):

Inducible Systemic Gcn1 Deletion in Mice Leads to Transient Body Weight Loss upon Tamoxifen Treatment Associated with Decrease of Fat and Liver Glycogen Storage.

Jun Liu, Shuya Kasai, Yota Tatara, Hiromi Yamazaki, Junsei Mimura, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Tsubasa Sato, Taku Ozaki, Kunikazu Tanji, Koichi Wakabayashi, Hayato Maeda, Hiroki Mizukami, Yasuhiro Shinkai, Yoshito Kumagai, Hirofumi Tomita, Ken Itoh.

  GCN1 is an evolutionarily-conserved ribosome-binding protein that mediates the amino acid starvation response as well as the ribotoxic stress response. We previously demonstrated that Gcn1 mutant mice lacking the GCN2-binding domain suffer from growth retardation and postnatal lethality via GCN2-independent mechanisms, while Gcn1-null mice die early in embryonic development. In this study, we explored the role of GCN1 in adult mice by generating tamoxifen-inducible conditional knockout (CKO) mice. Unexpectedly, the Gcn1 CKO mice showed body weight loss during tamoxifen treatment, which gradually recovered following its cessation. They also showed decreases in liver weight, hepatic glycogen and lipid contents, blood glucose and non-esterified fatty acids, and visceral white adipose tissue weight with no changes in food intake and viability. A decrease of serum VLDL suggested that hepatic lipid supply to the peripheral tissues was primarily impaired. Liver proteomic analysis revealed the downregulation of mitochondrial β-oxidation that accompanied increases of peroxisomal β-oxidation and aerobic glucose catabolism that maintain ATP levels. These findings show the involvement of GCN1 in hepatic lipid metabolism during tamoxifen treatment in adult mice.

Keywords:  GCN1; VLDL; body weight loss; lipid storage; tamoxifen toxicity

DOI:  https://doi.org/10.3390/ijms23063201
World J Hepatol. 2022 Feb 27. 14(2): 471-478

Glycogen hepatopathy in type-1 diabetes mellitus: A case report.

Yuvaraj Singh, Susant Gurung, Maya Gogtay.

  BACKGROUND: It has been studied that fluctuating glucose levels may superimpose glycated hemoglobin in determining the risk for diabetes mellitus (DM) complications. While non-alcoholic steatohepatitis (NASH) remains a predominant cause of elevated transaminases in Type 2 DM due to a strong underplay of metabolic syndrome, Type 1 DM can contrastingly affect the liver in a direct, benign, and reversible manner, causing Glycogen hepatopathy (GH) - with a good prognosis.CASE SUMMARY: A 50-year-old female with history of poorly controlled type 1 DM, status post cholecystectomy several years ago, and obesity presented with nausea, vomiting, and abdominal pain. Her vitals at the time of admission were stable. On physical examination, she had diffuse abdominal tenderness. Her finger-stick glucose was 612 mg/dL with elevated ketones and low bicarbonate. Her labs revealed abnormal liver studies: AST 1460 U/L, ALP: 682 U/L, ALP: 569 U/L, total bilirubin: 0.3mg/dL, normal total protein, albumin, and prothrombin time/ international normalized ratio (PT/INR). A magnetic resonance cholangiopancreatography (MRCP) demonstrated mild intra and extra-hepatic biliary ductal dilation without evidence of choledocholithiasis. She subsequently underwent a diagnostic ERCP which showed a moderately dilated CBD, for which a stent was placed. Studies for viral hepatitis, Wilson's Disease, alpha-1-antitrypsin, and iron panel came back normal. Due to waxing and waning transaminases during the hospital course, a liver biopsy was eventually done, revealing slightly enlarged hepatocytes that were PAS-positive, suggestive of glycogenic hepatopathy. With treatment of hyperglycemia and ensuing strict glycemic control, her transaminases improved, and she was discharged.
CONCLUSION: With a negative hepatocellular and cholestatic work-up, our patient likely had GH, a close differential for NASH but a poorly recognized entity. GH, first described in 1930 as a component of Mauriac syndrome, is believed to be due to glucose and insulin levels fluctuation. Dual echo magnetic resonance imaging sequencing and computed tomography scans of the liver are helpful to differentiate GH from NASH. Still, liver biopsy remains the gold standard for diagnosis. Biopsy predominantly shows intra-cellular glycogen deposition, with minimal or no steatosis or inflammation. As GH is reversible with good glycemic control, it should be one of the differentials in patients with brittle diabetes and elevated transaminases. GH, however, can cause a dramatic elevation in transaminases (50-1600 IU/L) alongside hepatomegaly and abdominal pain that would raise concern for acute liver injury leading to exhaustive work-up, as was in our patient above. Fluctuation in transaminases is predominantly seen during hyperglycemic episodes, and proper glycemic control is the mainstay of the treatment.

Keywords:  Case report; Diabetes; Glycogen; Hepatic; Mauriac; Steatosis; Type 1

DOI:  https://doi.org/10.4254/wjh.v14.i2.471
Methods Mol Biol. 2022 ;2442 205-214

Dissecting Context-Specific Galectin Binding Using Glycoengineered Cell Libraries.

Mathias Ingemann Nielsen, Hans H Wandall.

  The family of galectins has critical functions in a wide range of biological processes, primarily based on their broad interactions with proteins carrying β-galactoside-containing glycans. To understand the diversity of functions governed by galectins, it is essential to define the binding specificity of the carbohydrate recognition domain (CRDs) of the individual galectins. The binding specificity of galectins has primarily been examined with glycoarrays, but now the ability to probe and dissect binding to defined glycans in the context of a cellular membrane is facilitated by the generations of glycoengineered cell libraries with defined glyco-phenotypes. The following section will show how galectin specificities can be probed in the natural context of cellular surfaces using glycoengineered cell libraries, and how binding to glycoproteins can be measured in solution with fluorescence anisotropy.

Keywords:  Carbohydrate binding proteins; Galectin; Gene editing; Glycoengineering; Glycogenes; Glycosylation; Glycosyltransferases; Substrate specificity

DOI:  https://doi.org/10.1007/978-1-0716-2055-7_12