Insulin resistance is a complex condition where cells in the body, such as those in the liver, fat, and muscle, do not respond properly to insulin. Insulin resistance can be temporary or incurable, leading to increased insulin production known as hyperinsulinemia, which may contribute to obesity and eventually progress to type 2 diabetes. This mini-review elaborates the historical context of insulin discovery and its therapeutic use. It highlights the importance of insulin and insulin resistance in the context of metabolic diseases and discusses factors contributing to insulin resistance, such as poor diet, obesity, heredity, physical inactivity, and certain medical conditions. Lifestyle changes and pharmacological therapies are suggested for managing insulin resistance. The role of insulin in maintaining blood glucose levels and its resistance in various tissues, leading to compensatory hyperinsulinemia, are also discussed. It emphasizes the significance of understanding risk factors, lifestyle changes, and pharmacological interventions in preventing and treating insulin resistance. Additionally, it touches upon insulin's effects on glucose metabolism, the insulin resistance syndrome, and the clinical diagnostic entity known as metabolic syndrome. The impact of various factors on insulin secretion and production is also mentioned. Overall, it provides a comprehensive overview of insulin resistance, its consequences, and approaches to its management.

Keywords: Insulin resistance, type 2 diabetes, hyperinsulinemia, metabolic syndrome, Lifestyle changes

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1. Seong J, Kang JY, Sun JS, Kim KW. Hypothalamic inflammation and obesity: A mechanistic review. Archives of Pharmacal Research. 2019; 42: 383–392.
2. Wilcox G. Insulin and insulin resistance. Clinical Biochemist Reviews. 2005; 26(2): 19.
3. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiological Reviews. 2018. Physiol. Rev. Oct 2018; 98(4): 2133–2223. DOI: 10.1152/physrev.00063.2017.
4. Lebovitz HE. Insulin resistance: Definition and consequences. Experimental and Clinical Endocrinology & Diabetes. 2001; 109(2): S135–S148.
5. Kahn BB, Flier JS. Obesity and insulin resistance. The Journal of Clinical Investigation. 2000; 106(4): 473–481.
6. Rostène W, De Meyts P. Insulin: A 100-year-old discovery with a fascinating history. Endocrine Reviews. 2021; 42(5): 503–527.
7. Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865): 782–787.
8. Christesen HB, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, Brusgaard T, Massa O, Magnuson MA, Shiota C, Matschinsky FM, Barbetti F. The second activating glucokinase mutation (A456V) implications for glucose homeostasis and diabetes therapy. Am Diabetes Assoc. 2002; 51(4): 1240–1246.
9. Mäkinen KK. Gastrointestinal disturbances associated with the consumption of sugar alcohols with special consideration of xylitol: Scientific review and instructions for dentists and other health-care professionals. International Journal of Dentistry. 2016; 2016.
10. Jacobsen SH, Olesen S, Dirksen C, Jørgensen N, Bojsen-Møller K, Kielgast U, Worm D, Almdal T, Naver LS, Hvolris LE, Rehfeld JF, Wulff BS, Clausen TR, Hansen DL, Holst JJ, Madsbad S. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obesity Surgery. 2012; 22: 1084–1096.
11. Verberne AJM, Sabetghadam A, Korim WS. Neural pathways that control the glucose counterregulatory response. Frontiers in neuroscience. 2014; 8: 38.
12. Barber TM, Franks S. Obesity and polycystic ovary syndrome. Clinical Endocrinology. 2021; 95(4): 531–541.
13. Sedighi S, Akbari SAA, Afrakhteh M, Esteki T, Majd HA, Mahmoodi Z. Comparison of lifestyle in women with polycystic ovary syndrome and healthy women. Global Journal of Health Science. 2015; 7(1): 228.
14. Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2014; 19(7): 658.
15. Rojas LBA, Gomes MB. Metformin: An old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome. 2013; 5(1): 1–15.
16. Leturque A, Brot-Laroche E, Le Gall M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. American Journal of Physiology-Endocrinology and Metabolism. 2009; 296(5): E985–E992.
17. Von Ah Morano AE, Dorneles GP, Peres A, Lira FS. The role of glucose homeostasis on immune function in response to exercise: The impact of low or higher energetic conditions. Journal of Cellular Physiology. 2020; 235(4): 3169–3188.
18. Angelidi AM, Filippaios A, Mantzoros CS. Severe insulin resistance syndromes. The Journal of Clinical Investigation. 2021; 131(4).
19. Chan JC, Tong PC, Critchley JA. The insulin resistance syndrome: Mechanisms of clustering of cardiovascular risk. Semin Vasc. Med. Feb 2002; 2(1): 45–57. DOI: 10.1055/s-2002-23095.
20. Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga F. Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology. 2018; 17: 1–14.
21. Ginsberg HN. Insulin resistance and cardiovascular disease. The Journal of Clinical Investigation. 2000; 106(4): 453–458.
22. Prentki M, Matschinsky FM, Madiraju SRM. Metabolic signaling in fuel-induced insulin secretion. Cell Metabolism. 2013; 18(2): 162–185.
23. Lewis GF, Carpentier AC, Pereira S, Hahn M, Giacca A. Direct and indirect control of hepatic glucose production by insulin. Cell Metabolism. 2021; 33(4): 709–720.

Insulin resistance is a complex condition where cells in the body, such as those in the liver, fat, and muscle, do not respond properly to insulin. Insulin resistance can be temporary or incurable, leading to increased insulin production known as hyperinsulinemia, which may contribute to obesity and eventually progress to type 2 diabetes. This mini-review elaborates the historical context of insulin discovery and its therapeutic use. It highlights the importance of insulin and insulin resistance in the context of metabolic diseases and discusses factors contributing to insulin resistance, such as poor diet, obesity, heredity, physical inactivity, and certain medical conditions. Lifestyle changes and pharmacological therapies are suggested for managing insulin resistance. The role of insulin in maintaining blood glucose levels and its resistance in various tissues, leading to compensatory hyperinsulinemia, are also discussed. It emphasizes the significance of understanding risk factors, lifestyle changes, and pharmacological interventions in preventing and treating insulin resistance. Additionally, it touches upon insulin's effects on glucose metabolism, the insulin resistance syndrome, and the clinical diagnostic entity known as metabolic syndrome. The impact of various factors on insulin secretion and production is also mentioned. Overall, it provides a comprehensive overview of insulin resistance, its consequences, and approaches to its management.

Keywords: Insulin resistance, type 2 diabetes, hyperinsulinemia, metabolic syndrome, Lifestyle changes

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Seong J, Kang JY, Sun JS, Kim KW. Hypothalamic inflammation and obesity: A mechanistic review. Archives of Pharmacal Research. 2019; 42: 383–392.
2. Wilcox G. Insulin and insulin resistance. Clinical Biochemist Reviews. 2005; 26(2): 19.
3. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiological Reviews. 2018. Physiol. Rev. Oct 2018; 98(4): 2133–2223. DOI: 10.1152/physrev.00063.2017.
4. Lebovitz HE. Insulin resistance: Definition and consequences. Experimental and Clinical Endocrinology & Diabetes. 2001; 109(2): S135–S148.
5. Kahn BB, Flier JS. Obesity and insulin resistance. The Journal of Clinical Investigation. 2000; 106(4): 473–481.
6. Rostène W, De Meyts P. Insulin: A 100-year-old discovery with a fascinating history. Endocrine Reviews. 2021; 42(5): 503–527.
7. Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865): 782–787.
8. Christesen HB, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, Brusgaard T, Massa O, Magnuson MA, Shiota C, Matschinsky FM, Barbetti F. The second activating glucokinase mutation (A456V) implications for glucose homeostasis and diabetes therapy. Am Diabetes Assoc. 2002; 51(4): 1240–1246.
9. Mäkinen KK. Gastrointestinal disturbances associated with the consumption of sugar alcohols with special consideration of xylitol: Scientific review and instructions for dentists and other health-care professionals. International Journal of Dentistry. 2016; 2016.
10. Jacobsen SH, Olesen S, Dirksen C, Jørgensen N, Bojsen-Møller K, Kielgast U, Worm D, Almdal T, Naver LS, Hvolris LE, Rehfeld JF, Wulff BS, Clausen TR, Hansen DL, Holst JJ, Madsbad S. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obesity Surgery. 2012; 22: 1084–1096.
11. Verberne AJM, Sabetghadam A, Korim WS. Neural pathways that control the glucose counterregulatory response. Frontiers in neuroscience. 2014; 8: 38.
12. Barber TM, Franks S. Obesity and polycystic ovary syndrome. Clinical Endocrinology. 2021; 95(4): 531–541.
13. Sedighi S, Akbari SAA, Afrakhteh M, Esteki T, Majd HA, Mahmoodi Z. Comparison of lifestyle in women with polycystic ovary syndrome and healthy women. Global Journal of Health Science. 2015; 7(1): 228.
14. Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2014; 19(7): 658.
15. Rojas LBA, Gomes MB. Metformin: An old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome. 2013; 5(1): 1–15.
16. Leturque A, Brot-Laroche E, Le Gall M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. American Journal of Physiology-Endocrinology and Metabolism. 2009; 296(5): E985–E992.
17. Von Ah Morano AE, Dorneles GP, Peres A, Lira FS. The role of glucose homeostasis on immune function in response to exercise: The impact of low or higher energetic conditions. Journal of Cellular Physiology. 2020; 235(4): 3169–3188.
18. Angelidi AM, Filippaios A, Mantzoros CS. Severe insulin resistance syndromes. The Journal of Clinical Investigation. 2021; 131(4).
19. Chan JC, Tong PC, Critchley JA. The insulin resistance syndrome: Mechanisms of clustering of cardiovascular risk. Semin Vasc. Med. Feb 2002; 2(1): 45–57. DOI: 10.1055/s-2002-23095.
20. Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga F. Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology. 2018; 17: 1–14.
21. Ginsberg HN. Insulin resistance and cardiovascular disease. The Journal of Clinical Investigation. 2000; 106(4): 453–458.
22. Prentki M, Matschinsky FM, Madiraju SRM. Metabolic signaling in fuel-induced insulin secretion. Cell Metabolism. 2013; 18(2): 162–185.
23. Lewis GF, Carpentier AC, Pereira S, Hahn M, Giacca A. Direct and indirect control of hepatic glucose production by insulin. Cell Metabolism. 2021; 33(4): 709–720.