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Chemical Compound Review


Synonyms: Humuline, Insugen, Ultraphane, Humulin N, Humulin R, ...
J. Holmkvist, C.M. Lindgren, B. Isomaa, D. Tojjar, P. Almgren, E. Renström, V. Lyssenko, L. Groop, T. Tuomi, G. Berglund, J.P. Baillargeon, A.C. Carpentier, Melanie G. Cree, Arthur P. Sanford, Robert R. Wolfe, Beatrice Morio, Ting Qian, Asle Aarsland, David N. Herndon, Ricki Fram, Jennifer J. Zwetsloot, Jose Manuel Fernández-Real, Gema Frühbeck, Javier Gómez-Ambrosi, Esteban Gorostiaga, Mikel Izquierdo, Jose Maria Moreno-Navarrete, Lluis Forga, Fernando Idoate, Javier Ibañez, Cristina Martínez, Javier Salvador, Francisco Ortega, Wifredo Ricart, Carsten Schmitz-Peiffer, Christopher J. Mitchell, Ebru Gurisik, Uschi Braun, D. Ross Laybutt, Sakura Narasimhan, David J. Pedersen, Michael Leitges, Gregory J. Cooney, James G. Burchfield, Trevor J. Biden, Thomas Linn, Nedim Soydan, Julia Ehl, Michael Eckhard, Clemens Kunz, Britta Fischer, Reinhard G. Bretzel, Enrique Rozengurt, James Sinnett-Smith, Krisztina Kisfalvi, Priscilla Hollander, Hubert S. Chou, Dahong Yu, Giuseppe Murdolo, Peter Lönnroth, Lena Strindberg, Per-Anders Jansson, Mikaela Sjöstrand, Lars Lind, Soffia Gudbjörnsdóttir, Kent Lundholm, Marita Fouladiun, Ingvar Bosaeus, Peter Daneryd, Ulla Körner, Petra Sixt-Ammilon, Lena Gunnebo, Tracey McLaughlin, Gerald Reaven, Fahim Abbasi, Cindy Lamendola, Young-jai You, Jeongho Kim, David M. Raizen, Leon Avery, Marc G. Jeschke, Darren F. Boehning, Celeste C. Finnerty, David N. Herndon, Paul Norwood, Jean-Francois Yale, Richard England, Richard Riese, William Cefalu, John Teeter, Richard Dumas, K. Jeitler, A. Berghold, T.R. Pieber, K. Horvath, K. Neeser, A. Siebenhofer, T.W. Gratzer, Claudio Maffeis, Riccardo Manfredi, Teresa Benuzzi, Riccardo C. Bonadonna, Maddalena Trombetta, Silvia Sordelli, Monica Storti,  
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Disease relevance of Insulin


Psychiatry related information on Insulin

  • Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity [13].
  • Regression models were established to describe associations between fatness, fitness and physical activity and measures of insulin sensitivity (whole-body, fat and liver) as outcomes [14].

Chemical compound and disease context of Insulin


Associations of Insulin with other chemical compounds

  • Resveratrol, a SIRT1 activator, enhanced insulin sensitivity in vitro in a SIRT1-dependent manner and attenuated high-fat-diet-induced insulin resistance in vivo at a dose of 2.5 mg/kg/day [19].
  • We provide evidence that ephrin-A5 is required for glucose-stimulated insulin secretion [20].
  • Adiponectin-induced oxidants cause the oxidation/inhibition of protein-tyrosine phosphatase (PTP) 1B, one of the major phosphotyrosine phosphatases involved in the control of insulin receptor phosphorylation [21].
  • Insulin-stimulated glucose uptake increased significantly in FEN (4.3 +/- 0.6 vs. 4.5 +/- 0.7 PLA and 5.2 +/- 0.5 vs. 7.6 +/- 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003) [22].
  • Tacrolimus-induced diabetes in the rat seems to be mainly provoked by a decreased insulin gene transcription with little or no alteration of islet mass [23].
  • The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide [24].
  • We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23 [25].
  • EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice [26].
  • The metabolic activity in the first 2 h after injection was higher with ultra-fast insulin and insulin lispro than with human soluble insulin (AUC glucose infusion rate [GIR] 0-120 min: 915 +/- 301 and 781 +/- 174 vs 580 +/- 164 mg/kg; p < 0.05) [27].
  • SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2 [28].
  • The EGL-4 cGMP-dependent protein kinase functions downstream of insulin and TGF-beta in sensory neurons including ASI to control quiescence in response to food intake [29].
  • A standardized protocol of intravenous insulin before 18F-FDG injection in diabetic cancer patients was safe and effective in reducing glycemia [30].
  • These combined results strongly suggest that insulin induces ROS generation trough NADPH activation and that this ROS increase is required for the intracellular Ca2+ rise mediated by inositol 1,4,5-trisphosphate receptors [31].
  • The postintervention serum levels of osteocalcin were associated with both insulin sensitivity (r = 0.49; P = 0.03) and fasting triglycerides (r = -0.54; P = 0.01) [32].
  • Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1 [33].
  • In association with increased hepatic mFAO capacity, liver CPT1mt expression improved glucose tolerance and insulin response to a glucose load in HF/HS and ob/ob mice, showing increased insulin sensitivity, and corrected IR in ob/ob mice [34].

Gene context of Insulin

  • Ectopic expression of PTP-MEG2 in cells inhibited insulin-induced phosphorylation of the insulin receptor, while RNAi-mediated reduction of PTP-MEG2 transcript levels enhanced insulin action [35].
  • These experiments establish a new role for Abca1 in beta-cell cholesterol homeostasis and insulin secretion, and suggest that cholesterol accumulation may contribute to beta-cell dysfunction in type 2 diabetes [36].
  • Functional ablation of PKCepsilon selectively enhanced insulin release ex vivo from diabetic or lipid-pretreated islets and optimized the glucose-regulated lipid partitioning that amplifies the secretory response [37].
  • We propose that ASNA1 is an evolutionarily conserved modulator of insulin signaling [38].
  • It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKbeta, while improving insulin signalling in liver and muscle [39].
  • We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II [40].
  • In the second model, we examined the relative significance of insulin versus IGF1 receptors in islet growth by feeding high-fat diets to beta IRKO and beta-cell-specific IGF1 receptor knockout (beta IGFRKO) mice [41].
  • We conclude that genetic variation in the CACNA1E gene contributes to an increased risk of the development of type 2 diabetes by reducing insulin secretion [42].



  1. Exogenous insulin use and hypertension in adult patients with type 2 diabetes mellitus. Tseng, C.H. Arch. Intern. Med. (2006) [Pubmed]
  2. Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Hermans, G., Wilmer, A., Meersseman, W., Milants, I., Wouters, P.J., Bobbaers, H., Bruyninckx, F., Van den Berghe, G. Am. J. Respir. Crit. Care Med. (2007) [Pubmed]
  3. Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. McLaughlin, T., Abbasi, F., Lamendola, C., Reaven, G. Arch. Intern. Med. (2007) [Pubmed]
  4. Randomized study to characterize glycemic control and short-term pulmonary function in patients with type 1 diabetes receiving inhaled human insulin (exubera). Norwood, P., Dumas, R., Cefalu, W., Yale, J.F., England, R., Riese, R., Teeter, J. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  5. Effect of insulin on the inflammatory and acute phase response after burn injury. Jeschke, M.G., Boehning, D.F., Finnerty, C.C., Herndon, D.N. Crit. Care Med. (2007) [Pubmed]
  6. Insulin and the burned patient. Pidcoke, H.F., Wade, C.E., Wolf, S.E. Crit. Care Med. (2007) [Pubmed]
  7. Impact of steatosis on insulin secretion in chronic hepatitis C patients. Narita, R., Abe, S., Tabaru, A., Otsuki, M. Am. J. Gastroenterol. (2007) [Pubmed]
  8. Insulin sensitivity is correlated with subcutaneous but not visceral body fat in overweight and obese prepubertal children. Maffeis, C., Manfredi, R., Trombetta, M., Sordelli, S., Storti, M., Benuzzi, T., Bonadonna, R.C. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  9. Insulin-like signaling, nutrient homeostasis, and life span. Taguchi, A., White, M.F. Annu. Rev. Physiol. (2008) [Pubmed]
  10. A novel interaction between dietary composition and insulin secretion: effects on weight gain in the Quebec Family Study. Chaput, J.P., Tremblay, A., Rimm, E.B., Bouchard, C., Ludwig, D.S. Am. J. Clin. Nutr. (2008) [Pubmed]
  11. Effects of Intrabrachial metacholine infusion on muscle capillary recruitment and forearm glucose uptake during physiological hyperinsulinemia in obese, insulin-resistant individuals. Murdolo, G., Sjöstrand, M., Strindberg, L., Gudbjörnsdóttir, S., Lind, L., Lönnroth, P., Jansson, P.A. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  12. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis. Jeitler, K., Horvath, K., Berghold, A., Gratzer, T.W., Neeser, K., Pieber, T.R., Siebenhofer, A. Diabetologia (2008) [Pubmed]
  13. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Lundholm, K., Körner, U., Gunnebo, L., Sixt-Ammilon, P., Fouladiun, M., Daneryd, P., Bosaeus, I. Clin. Cancer Res. (2007) [Pubmed]
  14. Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity. Holt, H.B., Wild, S.H., Wareham, N., Ekelund, U., Umpleby, M., Shojaee-Moradie, F., Holt, R.I., Phillips, D.I., Byrne, C.D. Diabetologia (2007) [Pubmed]
  15. Low-dose rosiglitazone in patients with insulin-requiring type 2 diabetes. Hollander, P., Yu, D., Chou, H.S. Arch. Intern. Med. (2007) [Pubmed]
  16. Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects. Baillargeon, J.P., Carpentier, A.C. Diabetologia (2007) [Pubmed]
  17. Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes. Linn, T., Fischer, B., Soydan, N., Eckhard, M., Ehl, J., Kunz, C., Bretzel, R.G. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  18. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Rozengurt, E., Sinnett-Smith, J., Kisfalvi, K. Clin. Cancer Res. (2010) [Pubmed]
  19. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Sun, C., Zhang, F., Ge, X., Yan, T., Chen, X., Shi, X., Zhai, Q. Cell Metab. (2007) [Pubmed]
  20. EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Konstantinova, I., Nikolova, G., Ohara-Imaizumi, M., Meda, P., Kucera, T., Zarbalis, K., Wurst, W., Nagamatsu, S., Lammert, E. Cell (2007) [Pubmed]
  21. Redox-dependent and ligand-independent trans-activation of insulin receptor by globular adiponectin. Fiaschi, T., Buricchi, F., Cozzi, G., Matthias, S., Parri, M., Raugei, G., Ramponi, G., Chiarugi, P. Hepatology (2007) [Pubmed]
  22. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Cree, M.G., Zwetsloot, J.J., Herndon, D.N., Qian, T., Morio, B., Fram, R., Sanford, A.P., Aarsland, A., Wolfe, R.R. Ann. Surg. (2007) [Pubmed]
  23. Tacrolimus-induced diabetes in rats courses with suppressed insulin gene expression in pancreatic islets. Hernández-Fisac, I., Pizarro-Delgado, J., Calle, C., Marques, M., Sánchez, A., Barrientos, A., Tamarit-Rodriguez, J. Am. J. Transplant. (2007) [Pubmed]
  24. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Jiang, J., Au, M., Lu, K., Eshpeter, A., Korbutt, G., Fisk, G., Majumdar, A.S. Stem. Cells (2007) [Pubmed]
  25. SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity. Boström, P., Andersson, L., Rutberg, M., Perman, J., Lidberg, U., Johansson, B.R., Fernandez-Rodriguez, J., Ericson, J., Nilsson, T., Borén, J., Olofsson, S.O. Nat. Cell Biol. (2007) [Pubmed]
  26. Epidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice. Lee, H.Y., Yea, K., Kim, J., Lee, B.D., Chae, Y.C., Kim, H.S., Lee, D.W., Kim, S.H., Cho, J.H., Jin, C.J., Koh, D.S., Park, K.S., Suh, P.G., Ryu, S.H. J. Cell. Mol. Med. (2008) [Pubmed]
  27. A novel insulin formulation with a more rapid onset of action. Steiner, S., Hompesch, M., Pohl, R., Simms, P., Flacke, F., Mohr, T., Pfützner, A., Heinemann, L. Diabetologia (2008) [Pubmed]
  28. SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans. Neumann-Haefelin, E., Qi, W., Finkbeiner, E., Walz, G., Baumeister, R., Hertweck, M. Genes Dev. (2008) [Pubmed]
  29. Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. You, Y.J., Kim, J., Raizen, D.M., Avery, L. Cell Metab. (2008) [Pubmed]
  30. Impact of intravenous insulin on 18F-FDG PET in diabetic cancer patients. Roy, F.N., Beaulieu, S., Boucher, L., Bourdeau, I., Cohade, C. J. Nucl. Med. (2009) [Pubmed]
  31. NADPH oxidase and hydrogen peroxide mediate insulin-induced calcium increase in skeletal muscle cells. Espinosa, A., García, A., Härtel, S., Hidalgo, C., Jaimovich, E. J. Biol. Chem. (2009) [Pubmed]
  32. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. Fernández-Real, J.M., Izquierdo, M., Ortega, F., Gorostiaga, E., Gómez-Ambrosi, J., Moreno-Navarrete, J.M., Frühbeck, G., Martínez, C., Idoate, F., Salvador, J., Forga, L., Ricart, W., Ibañez, J. J. Clin. Endocrinol. Metab. (2009) [Pubmed]
  33. Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo. Parisi, F., Riccardo, S., Daniel, M., Saqcena, M., Kundu, N., Pession, A., Grifoni, D., Stocker, H., Tabak, E., Bellosta, P. BMC Biol. (2011) [Pubmed]
  34. Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis. Monsenego, J., Mansouri, A., Akkaoui, M., Lenoir, V., Esnous, C., Fauveau, V., Tavernier, V., Girard, J., Prip-Buus, C. J. Hepatology (2011) [Pubmed]
  35. Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cho, C.Y., Koo, S.H., Wang, Y., Callaway, S., Hedrick, S., Mak, P.A., Orth, A.P., Peters, E.C., Saez, E., Montminy, M., Schultz, P.G., Chanda, S.K. Cell Metab. (2006) [Pubmed]
  36. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Brunham, L.R., Kruit, J.K., Pape, T.D., Timmins, J.M., Reuwer, A.Q., Vasanji, Z., Marsh, B.J., Rodrigues, B., Johnson, J.D., Parks, J.S., Verchere, C.B., Hayden, M.R. Nat. Med. (2007) [Pubmed]
  37. Inhibition of PKCepsilon improves glucose-stimulated insulin secretion and reduces insulin clearance. Schmitz-Peiffer, C., Laybutt, D.R., Burchfield, J.G., Gurisik, E., Narasimhan, S., Mitchell, C.J., Pedersen, D.J., Braun, U., Cooney, G.J., Leitges, M., Biden, T.J. Cell Metab. (2007) [Pubmed]
  38. ASNA-1 positively regulates insulin secretion in C. elegans and mammalian cells. Kao, G., Nordenson, C., Still, M., Rönnlund, A., Tuck, S., Naredi, P. Cell (2007) [Pubmed]
  39. L-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity. Prada, P.O., Hirabara, S.M., de Souza, C.T., Schenka, A.A., Zecchin, H.G., Vassallo, J., Velloso, L.A., Carneiro, E., Carvalheira, J.B., Curi, R., Saad, M.J. Diabetologia (2007) [Pubmed]
  40. Differential activation of insulin receptor substrates 1 and 2 by insulin-like growth factor-activated insulin receptors. Denley, A., Carroll, J.M., Brierley, G.V., Cosgrove, L., Wallace, J., Forbes, B., Roberts, C.T. Mol. Cell. Biol. (2007) [Pubmed]
  41. Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance. Okada, T., Liew, C.W., Hu, J., Hinault, C., Michael, M.D., Krtzfeldt, J., Yin, C., Holzenberger, M., Stoffel, M., Kulkarni, R.N. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  42. Polymorphisms in the gene encoding the voltage-dependent Ca(2+) channel Ca (V)2.3 (CACNA1E) are associated with type 2 diabetes and impaired insulin secretion. Holmkvist, J., Tojjar, D., Almgren, P., Lyssenko, V., Lindgren, C.M., Isomaa, B., Tuomi, T., Berglund, G., Renström, E., Groop, L. Diabetologia (2007) [Pubmed]
  43. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Kaplan, D.D., Zimmermann, G., Suyama, K., Meyer, T., Scott, M.P. Genes Dev. (2008) [Pubmed]
  44. Insulin protein and proliferation in ductal cells in the transplanted pancreas of patients with type 1 diabetes and recurrence of autoimmunity. Martin-Pagola, A., Sisino, G., Allende, G., Dominguez-Bendala, J., Gianani, R., Reijonen, H., Nepom, G.T., Ricordi, C., Ruiz, P., Sageshima, J., Ciancio, G., Burke, G.W., Pugliese, A. Diabetologia (2008) [Pubmed]
  45. The role of pyruvate carboxylase in insulin secretion and proliferation in rat pancreatic beta cells. Xu, J., Han, J., Long, Y.S., Epstein, P.N., Liu, Y.Q. Diabetologia (2008) [Pubmed]
  46. Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines. Shukla, A., Grisouard, J., Ehemann, V., Hermani, A., Enzmann, H., Mayer, D. Endocr. Relat. Cancer (2009) [Pubmed]
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