S. R. Hubbard, The insulin receptor: both a prototypical and atypical receptor tyrosine kinase, Cold Spring Harb. Perspect. Biol, vol.5, p.8946, 2013.

S. Seino and G. I. Bell, Alternative splicing of human insulin receptor messenger RNA, Biochem. Biophys. Res. Commun, vol.159, pp.312-316, 1989.

F. Frasca, Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells, Mol. Cell. Biol, vol.19, pp.3278-3288, 1999.

D. A. Mcclain, Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action, Mol. Endocrinol, vol.5, pp.734-739, 1991.

Y. Yamaguchi, Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells, Endocrinology, vol.129, pp.2058-2066, 1991.

A. Denley, Structural determinants for high-affinity binding of insulinlike growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR, Mol. Endocrinol, vol.18, pp.2502-2512, 2004.

A. Belfiore, Insulin receptor isoforms in physiology and disease: an updated view, Endocr. Rev, vol.38, pp.379-431, 2017.

S. I. Taylor, Mutations in insulin-receptor gene in insulin-resistant patients, Diabetes Care, vol.13, pp.257-279, 1990.

J. M. Olefsky and G. M. Reaven, Decreased insulin binding to lymphocytes from diabetic subjects, J. Clin. Invest, vol.54, pp.1323-1328, 1974.

J. M. Olefsky and G. M. Reaven, Insulin binding in diabetes. Relationships with plasma insulin levels and insulin sensitivity, Diabetes, vol.26, pp.680-688, 1977.

A. Nagarajan, MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels, Nat. Commun, vol.7, p.12639, 2016.

R. Song, Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders, Nature, vol.494, pp.375-379, 2013.

H. Chettouh, Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors, Cancer Res, vol.73, pp.3974-3986, 2013.

P. Berhanu and J. M. Olefsky, Photoaffinity labeling of insulin receptors in viable cultured human lymphocytes. Demonstration of receptor shedding and degradation, Diabetes, vol.31, pp.410-417, 1982.

J. R. Gavin, D. N. Buell, and J. Roth, Water-soluble insulin receptors from human lymphocytes, Science, vol.178, pp.168-169, 1972.

V. Papa, An intact and functional soluble form of the insulin receptor is secreted by cultured cells, Endocrinology, vol.133, pp.1369-1376, 1993.

V. Pezzino, Identification and initial characterization of insulin receptorlike immunoreactivity in human plasma, J. Clin. Endocrinol. Metab, vol.74, pp.1116-1121, 1992.

M. Hiriart, Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes, Front Endocrinol, vol.5, p.95, 2014.

T. Obata, Soluble insulin receptor ectodomain is elevated in the plasma of patients with diabetes, Diabetes, vol.56, pp.2028-2035, 2007.

H. O. El-mesallamy, N. M. Hamdy, D. M. Mostafa, and A. I. Amin, The serine protease granzyme B as an inflammatory marker, in relation to the insulin receptor cleavage in human obesity and type 2 diabetes mellitus, J. Interferon Cytokine Res, vol.34, pp.179-186, 2014.

G. Evin and C. Hince, BACE1 as a therapeutic target in Alzheimer's disease: rationale and current status, Drugs Aging, vol.30, pp.755-764, 2013.

J. W. Creemers, Processing of beta-secretase by furin and other members of the proprotein convertase family, J. Biol. Chem, vol.276, pp.4211-4217, 2001.

R. Yan, P. Han, H. Miao, P. Greengard, and H. Xu, The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta-amyloid precursor protein (APP) substrate, J. Biol. Chem, vol.276, pp.36788-36796, 2001.

J. Walter, Phosphorylation regulates intracellular trafficking of betasecretase, J. Biol. Chem, vol.276, pp.14634-14641, 2001.

L. Rajendran, Alzheimer's disease beta-amyloid peptides are released in association with exosomes, Proc. Natl Acad. Sci. USA, vol.103, pp.11172-11177, 2006.

R. T. Turner, Subsite specificity of memapsin 2 (beta-secretase): implications for inhibitor design, Biochemistry, vol.40, pp.10001-10006, 2001.

J. L. Johnson, E. Chambers, and K. Jayasundera, Application of a bioinformatics-based approach to identify novel putative in vivo BACE1 substrates, Biomed. Eng. Comput. Biol, vol.5, pp.1-15, 2013.

P. J. Meakin, Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice, Biochem. J, vol.441, pp.285-296, 2012.

M. Oliverio, Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function, Nat. Cell Biol, vol.18, pp.328-336, 2016.

K. Plucinska, Neuronal human BACE1 knockin induces systemic diabetes in mice, Diabetologia, vol.59, pp.1513-1523, 2016.

M. Maesako, Effect of glycogen synthase kinase 3 beta-mediated presenilin 1 phosphorylation on amyloid beta production is negatively regulated by insulin receptor cleavage, Neuroscience, vol.177, pp.298-307, 2011.

K. Kasuga, H. Kaneko, M. Nishizawa, O. Onodera, and T. Ikeuchi, Generation of intracellular domain of insulin receptor tyrosine kinase by gammasecretase, Biochem. Biophys. Res. Commun, vol.360, pp.90-96, 2007.

S. A. Prigent, K. K. Stanley, and K. Siddle, Identification of epitopes on the human insulin receptor reacting with rabbit polyclonal antisera and mouse monoclonal antibodies, J. Biol. Chem, vol.265, pp.9970-9977, 1990.

R. Vassar, Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE, Science, vol.286, pp.735-741, 1999.

M. Poggi, Palmitoylation of TNF alpha is involved in the regulation of TNF receptor 1 signalling, Biochim. Biophys. Acta, vol.1833, pp.602-612, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01478341

Y. Hiraoka, Ectodomain shedding of TNF-alpha is enhanced by nardilysin via activation of ADAM proteases, Biochem. Biophys. Res. Commun, vol.370, pp.154-158, 2008.

I. Leconte, J. L. Carpentier, and E. Clauser, The functions of the human insulin receptor are affected in different ways by mutation of each of the four Nglycosylation sites in the beta subunit, J. Biol. Chem, vol.269, pp.18062-18071, 1994.

I. Qahwash, W. He, A. Tomasselli, R. F. Kletzien, and R. Yan, Processing amyloid precursor protein at the beta-site requires proper orientation to be accessed by BACE1, J. Biol. Chem, vol.279, pp.39010-39016, 2004.

R. T. Turner, L. Hong, G. Koelsch, A. K. Ghosh, and J. Tang, Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase), Biochemistry, vol.44, pp.105-112, 2005.

H. Kadowaki, Four mutant alleles of the insulin receptor gene associated with genetic syndromes of extreme insulin resistance, Biochem. Biophys. Res. Commun, vol.237, pp.516-520, 1997.

Y. Kawashima, Leprechaunism (Donohue syndrome): a case bearing novel compound heterozygous mutations in the insulin receptor gene, Endocr. J, vol.60, pp.107-112, 2013.

J. Liu, Insulin activates the insulin receptor to downregulate the PTEN tumour suppressor, Oncogene, vol.33, pp.3878-3885, 2014.

B. J. Robertson, J. M. Moehring, and T. J. Moehring, Defective processing of the insulin receptor in an endoprotease-deficient Chinese hamster cell strain is corrected by expression of mouse furin, J. Biol. Chem, vol.268, pp.24274-24277, 1993.

H. J. Lee, High glucose upregulates BACE1-mediated Abeta production through ROS-dependent HIF-1alpha and LXRalpha/ABCA1-regulated lipid raft reorganization in SK-N-MC cells, Sci. Rep, vol.6, p.36746, 2016.

T. Yuasa, Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells, Biochem. Biophys. Res. Commun, vol.445, pp.236-243, 2014.

C. Hattori, BACE1 interacts with lipid raft proteins, J. Neurosci. Res, vol.84, pp.912-917, 2006.

M. Ebina, Inhibition by KMI-574 leads to dislocalization of BACE1 from lipid rafts, J. Neurosci. Res, vol.87, pp.360-368, 2009.

J. Gustavsson, Localization of the insulin receptor in caveolae of adipocyte plasma membrane, Faseb. J, vol.13, pp.1961-1971, 1999.

B. Leibiger, Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells, Mol. Cell, vol.7, pp.559-570, 2001.

S. Uhles, T. Moede, B. Leibiger, P. O. Berggren, and I. B. Leibiger, Isoformspecific insulin receptor signaling involves different plasma membrane domains, J. Cell. Biol, vol.163, pp.1327-1337, 2003.

E. Choi, X. Zhang, C. Xing, and H. Yu, Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis, Cell, vol.166, pp.567-581, 2016.

V. Schmidt, SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity, J. Clin. Invest, vol.126, pp.2706-2720, 2016.

P. J. Meakin, Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice, Sci. Rep, vol.8, p.55, 2018.

K. Plucinska, Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes, J. Neurosci, vol.34, pp.10710-10728, 2014.

X. Yang and K. Qian, Protein O-GlcNAcylation: emerging mechanisms and functions, Nat. Rev. Mol. Cell. Biol, vol.18, pp.452-465, 2017.

K. Zhang, R. Yin, X. Yang, and . O-glcnac, A Bittersweet Switch in Liver. Front Endocrinol. (Lausanne), vol.5, p.221, 2014.

M. Sierant, Evaluation of BACE1 silencing in cellular models, Int. J. Alzheimers Dis, p.257403, 2009.

R. Yan, Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity, Nature, vol.402, pp.533-537, 1999.

R. Yan, J. B. Munzner, M. E. Shuck, and M. J. Bienkowski, BACE2 functions as an alternative alpha-secretase in cells, J. Biol. Chem, vol.276, pp.34019-34027, 2001.

J. T. Haas, Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression, Cell Metab, vol.15, pp.873-884, 2012.

M. D. Michael, Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction, Mol. Cell, vol.6, pp.87-97, 2000.

M. Foretz, Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state, J. Clin. Invest, vol.120, pp.2355-2369, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00495746

L. Morzyglod, Growth factor receptor binding protein 14 inhibition triggers insulin-induced mouse hepatocyte proliferation and is associated with hepatocellular carcinoma, Hepatology, vol.65, pp.1352-1368, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01606970

M. A. Soos, Monoclonal antibodies reacting with multiple epitopes on the human insulin receptor, Biochem. J, vol.235, pp.199-208, 1986.