Genetic Explication of Impaired Insulin Resistance in Genesis of Metabolic Diseases Impaired Insulin Resistance
Main Article Content
Keywords
Metabolic syndrome (MetS), Prediabetes, Insulin Resistance, Inflammation, Pathways, Regulatory Networks
Abstract
This study aims to investigate the role of impaired insulin resistance in the onset and progression of metabolic diseases such as prediabetes, diabetes, and cardiovascular diseases. Insulin resistance occurs when insulin is unable to effectively stimulate glucose uptake, and if the body is unable to produce sufficient insulin to compensate, type 2 diabetes may develop. This research endeavors to elucidate the molecular and genetic underpinnings of insulin resistance and its association with metabolic disorders. Employing various tools and databases, gene interaction data was procured through GeneMania, and pathway validation was conducted using KEGG. Construction of gene regulatory networks employed GEPHI 0.9.2, with centralities statistical analysis identifying hub genes. Enrichment analysis and literature validation substantiated the significance of these hubs, resulting in the refinement of the initially identified seven genes to five with interaction data. The implicated hub genes were discerned to play roles in inflammation, either directly or indirectly. Future prospects involve further genetic analysis across diverse populations, utilizing PCR to discern the allelic variations of these identified hub genes. Ultimately, this research may shed light on the underlying genetic and molecular mechanisms of insulin resistance and metabolic syndrome, and contribute to the development of targeted treatments for these conditions.
References
[1] A. Pérez-García, M. Torrecilla-Parra, M. Fernández-De Frutos, Y. Martín-Martín, V. Pardo-Marqués, and C. M. Ramírez, “Posttranscriptional Regulation of Insulin Resistance Implications for Metabolic Diseases,” Biomolecules, vol. 12, no. 2. Multidisciplinary Digital Publishing Institute, p. 208, Jan. 26, 2022. doi: 10.3390/biom12020208.
[2] L. Tian et al., “Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases,” Food Sci. Hum. Wellness, vol. 12, no. 4, pp. 959–974, 2023, doi: 10.1016/j.fshw.2022.10.018.
[3] American Diabetes Association, “Prediabetes | ADA,” 2020. https://diabetes.org/diabetes/prediabetes (accessed Mar. 13, 2023).
[4] Centers for Disease Control, “Prediabetes: Your Chance to Prevent Type 2 Diabetes | CDC,” Diabetes, 2018. https://www.cdc.gov/diabetes/basics/prediabetes.html (accessed Mar. 13, 2023).
[5] A. S. Wallace, D. Wang, J. I. Shin, and E. Selvin, “Screening and diagnosis of prediabetes and diabetes in us children and adolescents,” Pediatrics, vol. 146, no. 3, Sep. 2020, doi: 10.1542/PEDS.2020-0265.
[6] National Institute of Diabetes and Digestive and Kidney Diseases, “Insulin Resistance & Prediabetes | NIDDK,” National Institutes of Health, 2020. https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance (accessed Mar. 13, 2023).
[7] H. Sun et al., “IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045,” Diabetes Res. Clin. Pract., vol. 183, p. 109119, 2022, doi: 10.1016/j.diabres.2021.109119.
[8] “World Obesity Federation,” About Obesity, 2021. https://www.worldobesity.org/about/about-obesity (accessed Mar. 13, 2023).
[9] C. Lobstein, “World Obesity Federation Projections,” About Obesity, 2021. https://www.worldobesity.org/about/about-obesity (accessed Mar. 13, 2023).
[10] K. T. Mills et al., “Global disparities of hypertension prevalence and control,” Circulation, vol. 134, no. 6, pp. 441–450, Aug. 2016, doi: 10.1161/CIRCULATIONAHA.115.018912.
[11] “Cardiovascular Disease: Types, Causes & Symptoms,” 2022. https://my.clevelandclinic.org/health/diseases/21493-cardiovascular-disease (accessed Mar. 13, 2023).
[12] G. A. Roth et al., “Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017,” Lancet (London, England), vol. 392, no. 10159, pp. 1736–1788, Nov. 2018, doi: 10.1016/S0140-6736(18)32203-7.
[13] S. A. Lear and D. Gasevic, “Ethnicity and metabolic syndrome: Implications for assessment, management and prevention,” Nutrients, vol. 12, no. 1, Jan. 2020, doi: 10.3390/nu12010015.
[14] M. G. Saklayen, “The Global Epidemic of the Metabolic Syndrome,” Current Hypertension Reports, vol. 20, no. 2. Current Medicine Group LLC 1, pp. 1–8, Feb. 01, 2018. doi: 10.1007/s11906-018-0812-z.
[15] “American Heart Association. Why Metabolic Syndrome Matters,” 2020. https://www.heart.org/en/health-topics/metabolic-syndrome (accessed Mar. 13, 2023).
[16] A. R. Gosmanov, E. O. Gosmanova, and E. Dillard-Cannon, “Management of adult diabetic ketoacidosis,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, vol. 7. Dove Press, pp. 255–264, Jun. 30, 2014. doi: 10.2147/DMSO.S50516.
[17] T. Jelenik et al., “Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver,” Diabetes, vol. 66, no. 8, pp. 2241–2253, Aug. 2017, doi: 10.2337/db16-1147.
[18] C. Bouchard, “Gene-environment interactions in the etiology of obesity: Defining the fundamentals,” Obesity, vol. 16, no. SUPPL. 3, Dec. 2008, doi: 10.1038/oby.2008.528.
[19] B. V. K. S. Lakkakula, M. Thangavelu, and U. R. Godla, “Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: A systematic review,” Journal of Assisted Reproduction and Genetics, vol. 30, no. 7. Springer, pp. 883–895, Jul. 2013. doi: 10.1007/s10815-013-0030-1.
[20] Z. Dastani et al., “Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals,” PLoS Genet., vol. 8, no. 3, p. e1002607, Mar. 2012, doi: 10.1371/JOURNAL.PGEN.1002607.
[21] A. T. Kraja et al., “A bivariate genome-wide approach to metabolic syndrome: STAMPEED Consortium,” Diabetes, vol. 60, no. 4, pp. 1329–1339, Apr. 2011, doi: 10.2337/db10-1011.
[22] M. Franz et al., “GeneMANIA update 2018,” Nucleic Acids Res., vol. 46, no. W1, pp. W60–W64, Jul. 2018, doi: 10.1093/NAR/GKY311.
[23] B. Mathieu et al., “Gephi - The Open Graph Viz Platform.” 2008. Accessed: Feb. 24, 2023. [Online]. Available: https://gephi.org/
[24] P. Bonacich, “Some unique properties of eigenvector centrality,” Soc. Networks, vol. 29, no. 4, pp. 555–564, Oct. 2007, doi: 10.1016/j.socnet.2007.04.002.
[25] E. Estrada and N. Hatano, “Communicability in complex networks,” Phys. Rev. E - Stat. Nonlinear, Soft Matter Phys., vol. 77, no. 3, p. 036111, Mar. 2008, doi: 10.1103/PhysRevE.77.036111.
[26] M. Bastian, S. Heymann, and M. Jacomy, “Gephi: An Open Source Software for Exploring and Manipulating Networks,” Proc. Int. AAAI Conf. Web Soc. Media, vol. 3, no. 1, pp. 361–362, Mar. 2009, doi: 10.1609/icwsm.v3i1.13937.
[27] “ToppGene Suite.” p. 2170870, 2014. Accessed: Feb. 24, 2023. [Online]. Available: https://toppgene.cchmc.org/help/publications.jsp
[28] V. Kaimal, E. E. Bardes, S. C. Tabar, A. G. Jegga, and B. J. Aronow, “ToppCluster: A multiple gene list feature analyzer for comparative enrichment clustering and networkbased dissection of biological systems,” Nucleic Acids Res., vol. 38, no. SUPPL. 2, May 2010, doi: 10.1093/NAR/GKQ418.
[29] O. Escribano, M. Arribas, A. M. Valverde, and M. Benito, “IRS-3 mediates insulin-induced glucose uptake in differentiated IRS-2-/- brown adipocytes,” Mol. Cell. Endocrinol., vol. 268, no. 1–2, pp. 1–9, Mar. 2007, doi: 10.1016/j.mce.2006.12.039.
[30] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865, pp. 799–806, 2001, doi: 10.1038/414799a.
[31] V. T. Samuel and G. I. Shulman, “Mechanisms for insulin resistance: Common threads and missing links,” Cell, vol. 148, no. 5. Cell Press, pp. 852–871, Mar. 02, 2012. doi: 10.1016/j.cell.2012.02.017.
[32] S. Kobayashi, K. Maesato, H. Moriya, T. Ohtake, and T. Ikeda, “Insulin resistance in patients with chronic kidney disease,” Am. J. Kidney Dis., vol. 45, no. 2, pp. 275–280, Feb. 2005, doi: 10.1053/j.ajkd.2004.09.034.
[33] I. Shimizu et al., “Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents,” J. Clin. Invest., vol. 120, no. 5, pp. 1506–1514, May 2010, doi: 10.1172/JCI40096.
[34] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865. Nature Publishing Group, pp. 799–806, Dec. 13, 2001. doi: 10.1038/414799a.
[35] S. A. Cook et al., “Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction,” Eur. Heart J., vol. 31, no. 1, pp. 100–111, Jan. 2010, doi: 10.1093/eurheartj/ehp396.
[36] L. Rossetti, D. Smith, G. I. Shulman, D. Papachristou, and R. A. DeFronzo, “Correction of hyperglycemia with phlorizin normalizes tissues sensitivity to insulin in diabetic rats,” J. Clin. Invest., vol. 79, no. 5, pp. 1510–1515, May 1987, doi: 10.1172/JCI112981.
[37] “Advancing Heart, Lung, Blood, and Sleep Research & Innovation | NHLBI, NIH,” Natl. Hear. Lung Blood Inst., Accessed: Mar. 14, 2023. [Online]. Available: https://www.nhlbi.nih.gov/
[38] V. L. Roger et al., “Heart disease and stroke statistics-2011 update: A report from the American Heart Association,” Circulation, vol. 123, no. 4, pp. 18–209, 2011, doi: 10.1161/CIR.0b013e3182009701.
[39] B. F. Voight et al., “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis,” Nat. Genet., vol. 42, no. 7, pp. 579–589, Jun. 2010, doi: 10.1038/ng.609.
[40] J. Rung et al., “Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia,” Nat. Genet., vol. 41, no. 10, pp. 1110–1115, Sep. 2009, doi: 10.1038/ng.443.
[41] J. W. Knowles et al., “Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene,” J. Clin. Invest., vol. 125, no. 4, pp. 1739–1751, Apr. 2015, doi: 10.1172/JCI74692.
[42] G. Chen et al., “Genome-wide association study identifies novel loci association with fasting insulin and insulin resistance in African Americans,” Hum. Mol. Genet., vol. 21, no. 20, pp. 4530–4536, Oct. 2012, doi: 10.1093/hmg/dds282.
[43] L. C. Groop et al., “Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance,” J. Clin. Invest., vol. 84, no. 1, pp. 205–213, Jul. 1989, doi: 10.1172/JCI114142.
[44] E. Bugianesi et al., “Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: Sites and mechanisms,” Diabetologia, vol. 48, no. 4, pp. 634–642, Apr. 2005, doi: 10.1007/s00125-005-1682-x.
[45] P. E. Scherer, “Adipose tissue: From lipid storage compartment to endocrine organ,” in Diabetes, Jun. 2006, vol. 55, no. 6, pp. 1537–1545. doi: 10.2337/db06-0263.
[46] G. I. Shulman, “Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease,” N. Engl. J. Med., vol. 371, no. 12, pp. 1131–1141, Sep. 2014, doi: 10.1056/nejmra1011035.
[47] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865. Springer Science and Business Media LLC, pp. 799–806, Dec. 13, 2001. doi: 10.1038/414799a.
[48] M. P. Czech, “Insulin action and resistance in obesity and type 2 diabetes,” Nature Medicine, vol. 23, no. 7. Nature Publishing Group, pp. 804–814, Jul. 01, 2017. doi: 10.1038/nm.4350.
[49] N. Ouchi, J. L. Parker, J. J. Lugus, and K. Walsh, “Adipokines in inflammation and metabolic disease,” Nature Reviews Immunology, vol. 11, no. 2. Nature Publishing Group, pp. 85–97, Jan. 21, 2011. doi: 10.1038/nri2921.
[50] S. M. Huang et al., “An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors,” Proc. Natl. Acad. Sci. U. S. A., vol. 99, no. 12, pp. 8400–8405, Jun. 2002, doi: 10.1073/pnas.122196999.
[51] G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121. Nature Publishing Group, pp. 860–867, Dec. 13, 2006. doi: 10.1038/nature05485.
[52] J. Hirosumi et al., “A central, role for JNK in obesity and insulin resistance,” Nature, vol. 420, no. 6913, pp. 333–336, Nov. 2002, doi: 10.1038/nature01137.
[53] G. Boden, “Obesity and Free Fatty Acids,” Endocrinol. Metab. Clin. North Am., vol. 37, no. 3, pp. 635–646, Sep. 2008, doi: 10.1016/J.ECL.2008.06.007.
[54] D. Cai et al., “Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB,” Nat. Med., vol. 11, no. 2, pp. 183–190, Jan. 2005, doi: 10.1038/nm1166.
[55] C. Martinez Calejman et al., “mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis,” Nat. Commun., vol. 11, no. 1, pp. 1–16, Jan. 2020, doi: 10.1038/s41467-020-14430-w.
[56] S. Patel, B. W. Doble, K. MacAulay, E. M. Sinclair, D. J. Drucker, and J. R. Woodgett, “Tissue-Specific Role of Glycogen Synthase Kinase 3β in Glucose Homeostasis and Insulin Action,” Mol. Cell. Biol., vol. 28, no. 20, pp. 6314–6328, Oct. 2008, doi: 10.1128/mcb.00763-08.
[57] S. A. Muhammad, W. Raza, T. Nguyen, B. Bai, X. Wu, and J. Chen, “Cellular signaling pathways in insulin resistance-systems biology analyses of microarray dataset reveals new drug target gene signatures of type 2 diabetes mellitus,” Front. Physiol., vol. 8, no. JAN, p. 13, Jan. 2017, doi: 10.3389/fphys.2017.00013.
[58] B. Ke et al., “Inactivation of NF-κB p65 (RelA) in liver improves insulin sensitivity and inhibits cAMP/PKA pathway,” Diabetes, vol. 64, no. 10, pp. 3355–3362, Oct. 2015, doi: 10.2337/db15-0242.
[2] L. Tian et al., “Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases,” Food Sci. Hum. Wellness, vol. 12, no. 4, pp. 959–974, 2023, doi: 10.1016/j.fshw.2022.10.018.
[3] American Diabetes Association, “Prediabetes | ADA,” 2020. https://diabetes.org/diabetes/prediabetes (accessed Mar. 13, 2023).
[4] Centers for Disease Control, “Prediabetes: Your Chance to Prevent Type 2 Diabetes | CDC,” Diabetes, 2018. https://www.cdc.gov/diabetes/basics/prediabetes.html (accessed Mar. 13, 2023).
[5] A. S. Wallace, D. Wang, J. I. Shin, and E. Selvin, “Screening and diagnosis of prediabetes and diabetes in us children and adolescents,” Pediatrics, vol. 146, no. 3, Sep. 2020, doi: 10.1542/PEDS.2020-0265.
[6] National Institute of Diabetes and Digestive and Kidney Diseases, “Insulin Resistance & Prediabetes | NIDDK,” National Institutes of Health, 2020. https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance (accessed Mar. 13, 2023).
[7] H. Sun et al., “IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045,” Diabetes Res. Clin. Pract., vol. 183, p. 109119, 2022, doi: 10.1016/j.diabres.2021.109119.
[8] “World Obesity Federation,” About Obesity, 2021. https://www.worldobesity.org/about/about-obesity (accessed Mar. 13, 2023).
[9] C. Lobstein, “World Obesity Federation Projections,” About Obesity, 2021. https://www.worldobesity.org/about/about-obesity (accessed Mar. 13, 2023).
[10] K. T. Mills et al., “Global disparities of hypertension prevalence and control,” Circulation, vol. 134, no. 6, pp. 441–450, Aug. 2016, doi: 10.1161/CIRCULATIONAHA.115.018912.
[11] “Cardiovascular Disease: Types, Causes & Symptoms,” 2022. https://my.clevelandclinic.org/health/diseases/21493-cardiovascular-disease (accessed Mar. 13, 2023).
[12] G. A. Roth et al., “Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017,” Lancet (London, England), vol. 392, no. 10159, pp. 1736–1788, Nov. 2018, doi: 10.1016/S0140-6736(18)32203-7.
[13] S. A. Lear and D. Gasevic, “Ethnicity and metabolic syndrome: Implications for assessment, management and prevention,” Nutrients, vol. 12, no. 1, Jan. 2020, doi: 10.3390/nu12010015.
[14] M. G. Saklayen, “The Global Epidemic of the Metabolic Syndrome,” Current Hypertension Reports, vol. 20, no. 2. Current Medicine Group LLC 1, pp. 1–8, Feb. 01, 2018. doi: 10.1007/s11906-018-0812-z.
[15] “American Heart Association. Why Metabolic Syndrome Matters,” 2020. https://www.heart.org/en/health-topics/metabolic-syndrome (accessed Mar. 13, 2023).
[16] A. R. Gosmanov, E. O. Gosmanova, and E. Dillard-Cannon, “Management of adult diabetic ketoacidosis,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, vol. 7. Dove Press, pp. 255–264, Jun. 30, 2014. doi: 10.2147/DMSO.S50516.
[17] T. Jelenik et al., “Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver,” Diabetes, vol. 66, no. 8, pp. 2241–2253, Aug. 2017, doi: 10.2337/db16-1147.
[18] C. Bouchard, “Gene-environment interactions in the etiology of obesity: Defining the fundamentals,” Obesity, vol. 16, no. SUPPL. 3, Dec. 2008, doi: 10.1038/oby.2008.528.
[19] B. V. K. S. Lakkakula, M. Thangavelu, and U. R. Godla, “Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: A systematic review,” Journal of Assisted Reproduction and Genetics, vol. 30, no. 7. Springer, pp. 883–895, Jul. 2013. doi: 10.1007/s10815-013-0030-1.
[20] Z. Dastani et al., “Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals,” PLoS Genet., vol. 8, no. 3, p. e1002607, Mar. 2012, doi: 10.1371/JOURNAL.PGEN.1002607.
[21] A. T. Kraja et al., “A bivariate genome-wide approach to metabolic syndrome: STAMPEED Consortium,” Diabetes, vol. 60, no. 4, pp. 1329–1339, Apr. 2011, doi: 10.2337/db10-1011.
[22] M. Franz et al., “GeneMANIA update 2018,” Nucleic Acids Res., vol. 46, no. W1, pp. W60–W64, Jul. 2018, doi: 10.1093/NAR/GKY311.
[23] B. Mathieu et al., “Gephi - The Open Graph Viz Platform.” 2008. Accessed: Feb. 24, 2023. [Online]. Available: https://gephi.org/
[24] P. Bonacich, “Some unique properties of eigenvector centrality,” Soc. Networks, vol. 29, no. 4, pp. 555–564, Oct. 2007, doi: 10.1016/j.socnet.2007.04.002.
[25] E. Estrada and N. Hatano, “Communicability in complex networks,” Phys. Rev. E - Stat. Nonlinear, Soft Matter Phys., vol. 77, no. 3, p. 036111, Mar. 2008, doi: 10.1103/PhysRevE.77.036111.
[26] M. Bastian, S. Heymann, and M. Jacomy, “Gephi: An Open Source Software for Exploring and Manipulating Networks,” Proc. Int. AAAI Conf. Web Soc. Media, vol. 3, no. 1, pp. 361–362, Mar. 2009, doi: 10.1609/icwsm.v3i1.13937.
[27] “ToppGene Suite.” p. 2170870, 2014. Accessed: Feb. 24, 2023. [Online]. Available: https://toppgene.cchmc.org/help/publications.jsp
[28] V. Kaimal, E. E. Bardes, S. C. Tabar, A. G. Jegga, and B. J. Aronow, “ToppCluster: A multiple gene list feature analyzer for comparative enrichment clustering and networkbased dissection of biological systems,” Nucleic Acids Res., vol. 38, no. SUPPL. 2, May 2010, doi: 10.1093/NAR/GKQ418.
[29] O. Escribano, M. Arribas, A. M. Valverde, and M. Benito, “IRS-3 mediates insulin-induced glucose uptake in differentiated IRS-2-/- brown adipocytes,” Mol. Cell. Endocrinol., vol. 268, no. 1–2, pp. 1–9, Mar. 2007, doi: 10.1016/j.mce.2006.12.039.
[30] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865, pp. 799–806, 2001, doi: 10.1038/414799a.
[31] V. T. Samuel and G. I. Shulman, “Mechanisms for insulin resistance: Common threads and missing links,” Cell, vol. 148, no. 5. Cell Press, pp. 852–871, Mar. 02, 2012. doi: 10.1016/j.cell.2012.02.017.
[32] S. Kobayashi, K. Maesato, H. Moriya, T. Ohtake, and T. Ikeda, “Insulin resistance in patients with chronic kidney disease,” Am. J. Kidney Dis., vol. 45, no. 2, pp. 275–280, Feb. 2005, doi: 10.1053/j.ajkd.2004.09.034.
[33] I. Shimizu et al., “Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents,” J. Clin. Invest., vol. 120, no. 5, pp. 1506–1514, May 2010, doi: 10.1172/JCI40096.
[34] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865. Nature Publishing Group, pp. 799–806, Dec. 13, 2001. doi: 10.1038/414799a.
[35] S. A. Cook et al., “Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction,” Eur. Heart J., vol. 31, no. 1, pp. 100–111, Jan. 2010, doi: 10.1093/eurheartj/ehp396.
[36] L. Rossetti, D. Smith, G. I. Shulman, D. Papachristou, and R. A. DeFronzo, “Correction of hyperglycemia with phlorizin normalizes tissues sensitivity to insulin in diabetic rats,” J. Clin. Invest., vol. 79, no. 5, pp. 1510–1515, May 1987, doi: 10.1172/JCI112981.
[37] “Advancing Heart, Lung, Blood, and Sleep Research & Innovation | NHLBI, NIH,” Natl. Hear. Lung Blood Inst., Accessed: Mar. 14, 2023. [Online]. Available: https://www.nhlbi.nih.gov/
[38] V. L. Roger et al., “Heart disease and stroke statistics-2011 update: A report from the American Heart Association,” Circulation, vol. 123, no. 4, pp. 18–209, 2011, doi: 10.1161/CIR.0b013e3182009701.
[39] B. F. Voight et al., “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis,” Nat. Genet., vol. 42, no. 7, pp. 579–589, Jun. 2010, doi: 10.1038/ng.609.
[40] J. Rung et al., “Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia,” Nat. Genet., vol. 41, no. 10, pp. 1110–1115, Sep. 2009, doi: 10.1038/ng.443.
[41] J. W. Knowles et al., “Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene,” J. Clin. Invest., vol. 125, no. 4, pp. 1739–1751, Apr. 2015, doi: 10.1172/JCI74692.
[42] G. Chen et al., “Genome-wide association study identifies novel loci association with fasting insulin and insulin resistance in African Americans,” Hum. Mol. Genet., vol. 21, no. 20, pp. 4530–4536, Oct. 2012, doi: 10.1093/hmg/dds282.
[43] L. C. Groop et al., “Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance,” J. Clin. Invest., vol. 84, no. 1, pp. 205–213, Jul. 1989, doi: 10.1172/JCI114142.
[44] E. Bugianesi et al., “Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: Sites and mechanisms,” Diabetologia, vol. 48, no. 4, pp. 634–642, Apr. 2005, doi: 10.1007/s00125-005-1682-x.
[45] P. E. Scherer, “Adipose tissue: From lipid storage compartment to endocrine organ,” in Diabetes, Jun. 2006, vol. 55, no. 6, pp. 1537–1545. doi: 10.2337/db06-0263.
[46] G. I. Shulman, “Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease,” N. Engl. J. Med., vol. 371, no. 12, pp. 1131–1141, Sep. 2014, doi: 10.1056/nejmra1011035.
[47] A. R. Saltiel and C. R. Kahn, “Insulin signalling and the regulation of glucose and lipid metabolism,” Nature, vol. 414, no. 6865. Springer Science and Business Media LLC, pp. 799–806, Dec. 13, 2001. doi: 10.1038/414799a.
[48] M. P. Czech, “Insulin action and resistance in obesity and type 2 diabetes,” Nature Medicine, vol. 23, no. 7. Nature Publishing Group, pp. 804–814, Jul. 01, 2017. doi: 10.1038/nm.4350.
[49] N. Ouchi, J. L. Parker, J. J. Lugus, and K. Walsh, “Adipokines in inflammation and metabolic disease,” Nature Reviews Immunology, vol. 11, no. 2. Nature Publishing Group, pp. 85–97, Jan. 21, 2011. doi: 10.1038/nri2921.
[50] S. M. Huang et al., “An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors,” Proc. Natl. Acad. Sci. U. S. A., vol. 99, no. 12, pp. 8400–8405, Jun. 2002, doi: 10.1073/pnas.122196999.
[51] G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121. Nature Publishing Group, pp. 860–867, Dec. 13, 2006. doi: 10.1038/nature05485.
[52] J. Hirosumi et al., “A central, role for JNK in obesity and insulin resistance,” Nature, vol. 420, no. 6913, pp. 333–336, Nov. 2002, doi: 10.1038/nature01137.
[53] G. Boden, “Obesity and Free Fatty Acids,” Endocrinol. Metab. Clin. North Am., vol. 37, no. 3, pp. 635–646, Sep. 2008, doi: 10.1016/J.ECL.2008.06.007.
[54] D. Cai et al., “Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB,” Nat. Med., vol. 11, no. 2, pp. 183–190, Jan. 2005, doi: 10.1038/nm1166.
[55] C. Martinez Calejman et al., “mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis,” Nat. Commun., vol. 11, no. 1, pp. 1–16, Jan. 2020, doi: 10.1038/s41467-020-14430-w.
[56] S. Patel, B. W. Doble, K. MacAulay, E. M. Sinclair, D. J. Drucker, and J. R. Woodgett, “Tissue-Specific Role of Glycogen Synthase Kinase 3β in Glucose Homeostasis and Insulin Action,” Mol. Cell. Biol., vol. 28, no. 20, pp. 6314–6328, Oct. 2008, doi: 10.1128/mcb.00763-08.
[57] S. A. Muhammad, W. Raza, T. Nguyen, B. Bai, X. Wu, and J. Chen, “Cellular signaling pathways in insulin resistance-systems biology analyses of microarray dataset reveals new drug target gene signatures of type 2 diabetes mellitus,” Front. Physiol., vol. 8, no. JAN, p. 13, Jan. 2017, doi: 10.3389/fphys.2017.00013.
[58] B. Ke et al., “Inactivation of NF-κB p65 (RelA) in liver improves insulin sensitivity and inhibits cAMP/PKA pathway,” Diabetes, vol. 64, no. 10, pp. 3355–3362, Oct. 2015, doi: 10.2337/db15-0242.
Article Sidebar
Published
Jun 24, 2024
Article Details
How to Cite
Naveed Iqbal Soomro, & Syeda Marriam Bakhtiar. (2024). Genetic Explication of Impaired Insulin Resistance in Genesis of Metabolic Diseases: Impaired Insulin Resistance. Journal of Population Therapeutics and Clinical Pharmacology, 31(6), 2655-2669. https://doi.org/10.53555/jptcp.v31i6.6988
Section
Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Author Biographies
Naveed Iqbal Soomro
Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences,
Capital University of Science and Technology, Islamabad, Pakistan.
Syeda Marriam Bakhtiar
Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences,
Capital University of Science and Technology, Islamabad, Pakistan.
How to Cite
Naveed Iqbal Soomro, & Syeda Marriam Bakhtiar. (2024). Genetic Explication of Impaired Insulin Resistance in Genesis of Metabolic Diseases: Impaired Insulin Resistance. Journal of Population Therapeutics and Clinical Pharmacology, 31(6), 2655-2669. https://doi.org/10.53555/jptcp.v31i6.6988