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There is interest in expanding the therapeutic application of PDE4 inhibitors to metabolic disorders, as their chronic application induces weight loss in patients and animals and improves glucose handling in mouse models of obesity and diabetes. Unexpectedly, we have found that acute PDE4 inhibitor treatment induces a temporary increase, rather than a decrease, in blood glucose levels in mice. Blood glucose levels in postprandial mice increase rapidly upon drug injection, reaching a maximum after ~45 min, and returning to baseline within ~4 h. This transient blood glucose spike is replicated by several structurally distinct PDE4 inhibitors, suggesting that it is a class effect of PDE4 inhibitors. PDE4 inhibitor treatment does not reduce serum insulin levels, and the subsequent injection of insulin potently reduces PDE4 inhibitor-induced blood glucose levels, suggesting that the glycemic effects of PDE4 inhibition are independent of changes in insulin secretion and\/or sensitivity. Conversely, PDE4 inhibitors induce a rapid reduction in skeletal muscle glycogen levels and potently inhibit the uptake of 2-deoxyglucose into muscle tissues. This suggests that reduced glucose uptake into muscle tissue is a significant contributor to the transient glycemic effects of PDE4 inhibitors in mice.<\/jats:p>","DOI":"10.3390\/ijms24043260","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:01:45Z","timestamp":1675825305000},"page":"3260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acute PDE4 Inhibition Induces a Transient Increase in Blood Glucose in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0062-7359","authenticated-orcid":false,"given":"Daniel","family":"Irelan","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-751X","authenticated-orcid":false,"given":"Peter","family":"Lochmaier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Will","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ileana V.","family":"Aragon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila","family":"Rachek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Abou Saleh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-9060","authenticated-orcid":false,"given":"Wito","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Center for Lung Biology, Whiddon College of Medicine, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1055\/s-0034-1389955","article-title":"Compartmentalization of cAMP signaling in adipogenesis, lipogenesis, and lipolysis","volume":"46","author":"Rogne","year":"2014","journal-title":"Horm. Metab. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R93","DOI":"10.1530\/JME-15-0316","article-title":"Targeting cAMP\/PKA pathway for glycemic control and type 2 diabetes therapy","volume":"57","author":"Yang","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bouchez, C., and Devin, A. (2019). Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): A Complex Relationship Regulated by the cAMP\/PKA Signaling Pathway. Cells, 8.","DOI":"10.3390\/cells8040287"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0950-351X(05)80207-1","article-title":"Control of glycaemia","volume":"7","author":"Gerich","year":"1993","journal-title":"Bailli\u00e8res Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/BF01799497","article-title":"Mechanisms of blood glucose homeostasis","volume":"13","author":"Hers","year":"1990","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dimitriadis, G., Maratou, E., Kountouri, A., Board, M., and Lambadiari, V. (2021). Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients, 13.","DOI":"10.3390\/nu13010159"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/978-90-481-3271-3_13","article-title":"Cyclic AMP signaling in pancreatic islets","volume":"654","author":"Furman","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of hepatic glucose metabolism in health and disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41573-019-0033-4","article-title":"Therapeutic targeting of 3\u2032,5\u2032-cyclic nucleotide phosphodiesterases: Inhibition and beyond","volume":"18","author":"Baillie","year":"2019","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.biochem.76.060305.150444","article-title":"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling","volume":"76","author":"Conti","year":"2007","journal-title":"Annu. Rev. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1042\/BJ20050030","article-title":"Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are differentially expressed and regulated in rat tissue","volume":"388","author":"Richter","year":"2005","journal-title":"Biochem. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1074\/jbc.R200029200","article-title":"Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling","volume":"278","author":"Conti","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1124\/pharmrev.120.000273","article-title":"The Molecular Biology of Phosphodiesterase 4 Enzymes as Pharmacological Targets: An Interplay of Isoforms, Conformational States, and Inhibitors","volume":"73","author":"Paes","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10594","DOI":"10.1021\/acs.jmedchem.9b02170","article-title":"Advances in the Development of Phosphodiesterase-4 Inhibitors","volume":"63","author":"Peng","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3389\/fphar.2018.01048","article-title":"Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases","volume":"9","author":"Li","year":"2018","journal-title":"Front Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1517\/14728222.2013.818656","article-title":"PDE4 as a target for cognition enhancement","volume":"17","author":"Richter","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_17","first-page":"197","article-title":"Phosphodiesterase 4 and its inhibitors in inflammatory diseases","volume":"35","author":"Jin","year":"2012","journal-title":"Chang. Gung. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1161\/01.RES.0000261934.56938.38","article-title":"cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: A molecular toolbox for generating compartmentalized cAMP signaling","volume":"100","author":"Houslay","year":"2007","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S1359-6446(05)03622-6","article-title":"Keynote review: Phosphodiesterase-4 as a therapeutic target","volume":"10","author":"Houslay","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1517\/14728222.9.6.1283","article-title":"Phosphodiesterase-4 as a potential drug target","volume":"9","author":"Zhang","year":"2005","journal-title":"Expert Opin. Targets"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/obr.12385","article-title":"Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders","volume":"17","author":"Wu","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cell.2012.01.017","article-title":"Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases","volume":"148","author":"Park","year":"2012","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2147\/DMSO.S182953","article-title":"Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight\/obesity involve age-associated fat mass loss-results of an exploratory study","volume":"12","author":"Muo","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E1720","DOI":"10.1210\/jc.2011-2886","article-title":"Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus","volume":"97","author":"Wouters","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/rheumatology\/keab474","article-title":"Effect of the phosphodiesterase 4 inhibitor apremilast on cardiometabolic outcomes in psoriatic disease\u2014Results of the Immune Metabolic Associations in Psoriatic Arthritis study","volume":"61","author":"Ferguson","year":"2021","journal-title":"Rheumatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/1346-8138.15293","article-title":"Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers","volume":"47","author":"Mazzilli","year":"2020","journal-title":"J. Derm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13048-015-0161-3","article-title":"Short term monotherapy with GLP-1 receptor agonist liraglutide or PDE 4 inhibitor roflumilast is superior to metformin in weight loss in obese PCOS women: A pilot randomized study","volume":"8","author":"Jensterle","year":"2015","journal-title":"J. Ovarian Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/dom.12839","article-title":"The PDE4 inhibitor roflumilast reduces weight gain by increasing energy expenditure and leads to improved glucose metabolism","volume":"19","author":"Mollmann","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1007\/s00125-012-2632-z","article-title":"The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db\/db mice","volume":"55","author":"Vollert","year":"2012","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114477","DOI":"10.1016\/j.bcp.2021.114477","article-title":"Inhibition of cAMP-phosphodiesterase 4 (PDE4) potentiates the anesthetic effects of Isoflurane in mice","volume":"186","author":"Aragon","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1042\/BCJ20210212","article-title":"The cAMP-phosphodiesterase 4 (PDE4) controls \u03b2-adrenoceptor- and CFTR-dependent saliva secretion in mice","volume":"478","author":"Boyd","year":"2021","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12533","DOI":"10.1096\/fj.202001016RR","article-title":"PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice","volume":"34","author":"McDonough","year":"2020","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114158","DOI":"10.1016\/j.bcp.2020.114158","article-title":"Inhibition of type 4 cAMP-phosphodiesterases (PDE4s) in mice induces hypothermia via effects on behavioral and central autonomous thermoregulation","volume":"180","author":"McDonough","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Boyd, A., Aragon, I.V., Rich, J., McDonough, W., Oditt, M., Irelan, D., Fiedler, E., Abou Saleh, L., and Richter, W. (2021). Assessment of PDE4 Inhibitor-Induced Hypothermia as a Correlate of Nausea in Mice. Biology, 10.","DOI":"10.3390\/biology10121355"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/B978-0-444-64074-1.00037-9","article-title":"Body temperature regulation and anesthesia","volume":"157","author":"Lenhardt","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/pr.55.1.7","article-title":"Pharmacological Agents That Directly Modulate Insulin Secretion","volume":"55","author":"Doyle","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1742-7843.2011.00699.x","article-title":"\u03b12-Adrenoceptor Regulation of Blood Glucose Homeostasis","volume":"108","author":"Fagerholm","year":"2011","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2337\/db16-1166","article-title":"Endogenous \u03b12A-Adrenoceptor\u2013Operated Sympathoadrenergic Tones Attenuate Insulin Secretion via cAMP\/TRPM2 Signaling","volume":"66","author":"Ito","year":"2017","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s41401-019-0305-x","article-title":"\u03b1 1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation","volume":"41","author":"Xin","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_40","first-page":"E162","article-title":"Regulation of alpha 2-adrenergic receptor expression and signaling in pancreatic beta-cells","volume":"269","author":"Hamamdzic","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22430","DOI":"10.1074\/jbc.M803306200","article-title":"Critical role of PDE4D in beta2-adrenoceptor-dependent cAMP signaling in mouse embryonic fibroblasts","volume":"283","author":"Bruss","year":"2008","journal-title":"J Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/CIRCRESAHA.107.167817","article-title":"Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: Role of phosphodiesterases","volume":"102","author":"Leroy","year":"2008","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1161\/01.RES.0000218493.09370.8e","article-title":"A specific pattern of phosphodiesterases controls the cAMP signals generated by different Gs-coupled receptors in adult rat ventricular myocytes","volume":"98","author":"Rochais","year":"2006","journal-title":"Circ Res"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1073\/pnas.262787199","article-title":"beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi","volume":"100","author":"Baillie","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pratt, E.P.S., Harvey, K.E., Salyer, A.E., and Hockerman, G.H. (2019). Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic \u03b2-cells. PLoS ONE, 14.","DOI":"10.1101\/593418"},{"key":"ref_46","first-page":"898","article-title":"Modulation of cyclic nucleotides and cyclic nucleotide phosphodiesterases in pancreatic islet beta-cells and intestinal L-cells as targets for treating diabetes mellitus","volume":"7","author":"Furman","year":"2006","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00125-003-1176-7","article-title":"Cyclic nucleotide phosphodiesterases in pancreatic islets","volume":"46","author":"Pyne","year":"2003","journal-title":"Diabetologia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.2337\/db11-0571","article-title":"Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: Induction of renal and intestinal gluconeogenesis by glucagon","volume":"60","author":"Mutel","year":"2011","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1007\/s00125-016-3955-y","article-title":"Glucagon: Acute actions on hepatic metabolism","volume":"59","author":"Miller","year":"2016","journal-title":"Diabetologia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1046\/j.1440-1681.2001.03440.x","article-title":"Type IV Phosphodiesterase Inhibitor Suppresses Insulin-Dependent Myocardial Glucose Uptake","volume":"28","author":"Imahashi","year":"2001","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1007\/s00259-002-0870-x","article-title":"Rolipram depresses [3H]2-deoxyglucose uptake in mouse brain and heart in vivo","volume":"29","author":"Ishikawa","year":"2002","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00210-013-0860-5","article-title":"\u03b22-adrenoceptor agonists can both stimulate and inhibit glucose uptake in mouse soleus muscle through ligand-directed signalling","volume":"386","author":"Ngala","year":"2013","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/sj.bjp.0706626","article-title":"Multiple signalling pathways involved in\u03b22-adrenoceptor-mediated glucose uptake in rat skeletal muscle cells","volume":"147","author":"Nevzorova","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","first-page":"576","article-title":"Isoproterenol- and epinephrine-induced changes in blood glucose and tissue glycogen levels in normal and diabetic rats: The influence of alteration in endogenous insulin levels and state of nourishment","volume":"193","author":"Potter","year":"1975","journal-title":"J. Pharm. Exp."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16557","DOI":"10.1016\/S0021-9258(19)85455-8","article-title":"GLUT4 phosphorylation and inhibition of glucose transport by dibutyryl cAMP","volume":"268","author":"Piper","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1073\/pnas.89.8.3493","article-title":"GLUT4 facilitates insulin stimulation and cAMP-mediated inhibition of glucose transport","volume":"89","author":"Lawrence","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11427-007-0088-z","article-title":"Insulin sensitivity and inhibition by forskolin, dipyridamole and pentobarbital of glucose transport in three L6 muscle cell lines","volume":"50","author":"Niu","year":"2007","journal-title":"Sci. China Ser. C Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/15548627.2015.1042195","article-title":"HK2\/hexokinase-II integrates glycolysis and autophagy to confer cellular protection","volume":"11","author":"Tan","year":"2015","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/cdd.2014.173","article-title":"Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy","volume":"22","author":"Roberts","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1242\/jeb.00241","article-title":"Isozymes of mammalian hexokinase: Structure, subcellular localization and metabolic function","volume":"206","author":"Wilson","year":"2003","journal-title":"J. Exp. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2337\/diabetes.50.6.1253","article-title":"Hexokinase Isozyme Distribution in Human Skeletal Muscle","volume":"50","author":"Ritov","year":"2001","journal-title":"Diabetes"},{"key":"ref_62","first-page":"1978","article-title":"Mechanistic Insights on Human Phosphoglucomutase Revealed by Transition Path Sampling and Molecular Dynamics Calculations","volume":"24","author":"Fernandes","year":"2017","journal-title":"Chem.\u2013A Eur. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1440-1681.2005.04190.x","article-title":"GLUCOSE PHOSPHORYLATION AS A BARRIER TO MUSCLE GLUCOSE UPTAKE","volume":"32","author":"Fueger","year":"2005","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1749-6632.2002.tb04278.x","article-title":"Regulation of Fat Metabolism in Skeletal Muscle","volume":"967","author":"Jeukendrup","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1002\/1873-3468.13070","article-title":"Of mice and men\u2014Environmental temperature, body temperature, and treatment of obesity","volume":"592","author":"Reitman","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1038\/sj.embor.7400422","article-title":"Of mice and men","volume":"6","author":"Demetrius","year":"2005","journal-title":"EMBO Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E1476","DOI":"10.1210\/jc.2014-1430","article-title":"Phosphodiesterase 4 Inhibition as a Potential New Therapeutic Target in Obese Women With Polycystic Ovary Syndrome","volume":"99","author":"Jensterle","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","first-page":"44","article-title":"Accuracy of 5 Point-of-Care Glucometers in C57BL\/6J Mice","volume":"57","author":"Morley","year":"2018","journal-title":"JAALAS"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"25465","DOI":"10.1038\/srep25465","article-title":"Evaluation of the appropriateness of using glucometers for measuring the blood glucose levels in mice","volume":"6","author":"Togashi","year":"2016","journal-title":"Sci. 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