Perspectives of application of intranasally administered insulin for correction of metabolic and hormonal disorders in diabetes mellitus and metabolic syndrome

Close metadata

Recommended articles:

Impact of SGLT2 inhibitors on erythropoiesis and iron exchange in patients with diabetes mellitus and chronic heart failure. Russian Journal of Preventive Medicine. 2024;(5):103-110

Incidence of carbohydrate metabolism disorder in iron overload of different etiology. Russian Journal of Preventive Medicine. 2024;(5):111-117

Predictors of effective complex physiotherapy in patients with skin involution. Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2024;(1):13-20

Fatal case of rhinocerebral mucormycosis on the background of type II diabetes mellitus. Russian Journal of Archive of Pathology. 2024;(3):52-58

Sir Charles Bell (1774—1842) and his contribution to neurology (the 250th anniversary of the birth). S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(5):128-132

Endarterectomy from superficial femoral artery in patients with type 2 diabetes mellitus. Russian Journal of Cardiology and Cardiovascular Surgery. 2024;(3):285-293

Evaluation of revascularization efficiency using near-infrared oximetry in patients with diabetic foot syndrome. Pirogov Russian Journal of Surgery. 2024;(6):20-27

Serum uric acid — a metabolic marker of non-alcoholic fatty liver disease. Russian Journal of Evidence-Based Gastroenterology. 2024;(2):36-42

Assessment of the condition of organs and tissues of the oral cavity in people with dentition defects against the background of metabolic syndrome. Stomatology. 2024;(3):31-38

Features of the oral microbiota in patients with type II diabetes in the background of dental implantation. Russian Journal of Stomatology. 2024;(2):21-26

In recent years, the possibility of using intranasally administered insulin to treat Alzheimer’s disease and other cognitive disorders has been widely studied. At the same time, the possibility of its use in the treatment of diabetes mellitus is practically not investigated, which is due to the insufficient study of the molecular mechanisms of its action on the hormonal and metabolic status of the organism. The review discusses literature data and the results of our own research on the role of insulin in the central regulation of energy homeostasis, as well as on the experience of using intranasally administered insulin to correct eating disorders and metabolic and hormonal dysfunctions developing under conditions of experimental diabetes mellitus and metabolic syndrome. In studies involving healthy volunteers, various effects of intranasally administered insulin were shown, including effects on cognitive function, eating behavior and weight loss, and the gender specificity of its action was found. In the course of numerous studies of intranasally administered insulin in animal models of diabetes mellitus, not only stabilization of carbohydrate homeostasis was shown, but also a positive effect in the form of restoration of the functional activity of insulin signaling pathways in the hypothalamus and other parts of the brain. We have presented and analyzed data on the systemic effects of intranasally administered insulin in rodents with experimental models of diabetes mellitus, as well as in healthy individuals.

Keywords:

Insulin

intranasal administration

diabetes mellitus

metabolic syndrome

brain

insulin resistance

energy metabolism

thyroid system

Authors:

Shpakov A.O.

Laboratoriia molekuliarnoĭ éndokrinologii Instituta évoliutsionnoĭ fiziologii i biokhimii im. I.M. Sechenova RAN, Sankt-Peterburg

Derkach K.V.

Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, St.-Petersburg, Russia

Surkova E.V.

FGBU Éndokrinologicheskiĭ nauchnyĭ tsentr MZ RF, Moskva

Bespalov A.I.

Endocrinology Research Centre, Moscow, Russia

List of references:

Shpakov AO, Derkach KV. Gormonal’nye sistemy mozga i sakharnyy diabet 2-go tipa. Saint-Petersburg: Izdatel’stvo Politekhnicheskogo universiteta; 2015. (In Russ.)
Gizurarson S, Bechgaard E. Intranasal administration of insulin to humans. Diabetes Res Clin Pract. 1991;12(2):71-84. https://doi.org/10.1016/0168-8227(91)90083-p
Hirai S, Ikenaga T, Matsuzawa T. Nasal Absorption of Insulin in Dogs. Diabetes. 1978;27(3):296-299 https://doi.org/10.2337/diab.27.3.296
Frauman A, Buchanan R, Jerumus G, Louis W. Intranasal insulin (INI) treatment of type I diabetes: clinical and immunologic effects using two different absorption enhancing adjuvants. Diabetes Res Clin Pract. 1988;5(Suppl 1):S162.
Derkach KV, Ivantsov AO, Chistyakova OV, et al. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome. Biull Eksp Biol Med. 2017;163(2):144-149. (In Russ.)
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69(1):29-38. https://doi.org/10.1001/archneurol.2011.233
Baskin D. Insulin In The Brain. Annu Rev Physiol. 1987;49(1):335-347. https://doi.org/10.1146/annurev.ph.49.030187.002003
Porte Jr D, Seeley RJ, Woods SC, et al. Obesity, diabetes and the central nervous system. Diabetologia. 1998;41(8):863-881. https://doi.org/10.1007/s001250051002
Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nature Med. 2002;8(12):1376-1382. https://doi.org/10.1038/nm1202-798
Hallschmid M, Benedict C, Schultes B, et al. Intranasal Insulin Reduces Body Fat in Men but not in Women. Diabetes. 2004;53(11):3024-3029. https://doi.org/10.2337/diabetes.53.11.3024
Born J, Lange T, Kern W, et al. Sniffing neuropeptides: a transnasal approach to the human brain. Nature Neuroscience. 2002;5(6):514-516. https://doi.org/10.1038/nn0602-849
Clegg DJ, Riedy CA, Smith KAB, et al. Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats. Diabetes. 2003;52(3):682-687. https://doi.org/10.2337/diabetes.52.3.682
Hallschmid M, Benedict C, Schultes B, et al. Obese men respond to cognitive but not to catabolic brain insulin signaling. Int J Obes (Lond). 2008;32(2):275-282. https://doi.org/10.1038/sj.ijo.0803722
Jauch-Chara K, Friedrich A, Rezmer M, et al. Intranasal insulin suppresses food intake via enhancement of brain energy levels in humans. Diabetes. 2012;61(9):2261-2268. https://doi.org/10.2337/db12-0025
Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron. 2011;69(4):664-679. https://doi.org/10.1016/j.neuron.2011.02.016
Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci. 2011;15(1):37-46. https://doi.org/10.1016/j.tics.2010.11.001
Appelhans BM. Neurobehavioral inhibition of reward-driven feeding: implications for dieting and obesity. Obesity (Silver Spring). 2009;17(4):640-647. https://doi.org/10.1038/oby.2008.638
Lathe R. Hormones and the hippocampus. J Endocrinol. 2001;169(2):205-231. https://doi.org/10.1677/joe.0.1690205
Figlewicz DP, Szot P, Chavez M, et al. Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra. Brain Res. 1994;644(2):331-334. https://doi.org/10.1016/0006-8993(94)91698-5
Guthoff M, Grichisch Y, Canova C, et al. Insulin modulates food-related activity in the central nervous system. J Clin Endocrinol Metab. 2010;95(2):748-755. https://doi.org/10.1210/jc.2009-1677
Clegg DJ, Brown LM, Woods SC, Benoit SC. Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin. Diabetes. 2006;55(4):978-987. https://doi.org/10.2337/diabetes.55.04.06.db05-1339
Krug R, Benedict C, Born J, Hallschmid M. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory. J Clin Endocrinol Metab. 2010;95(12):E468-472. https://doi.org/10.1210/jc.2010-0744
Hallschmid M, Higgs S, Thienel M, et al. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women. Diabetes. 2012;61(4):782-789. https://doi.org/10.2337/db11-1390.
Koch L, Wunderlich FT, Seibler J, et al. Central insulin action regulates peripheral glucose and fat metabolism in mice. J Clin Invest. 2008;118(6):2132-2147. https://doi.org/10.1172/JCI31073
Heni M, Wagner R, Kullmann S, et al. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014;63(12):4083-4088. https://doi.org/10.2337/db14-0477
Dash S, Xiao C, Morgantini C, et al. Intranasal insulin suppresses endogenous glucose production in humans compared with placebo in the presence of similar venous insulin concentrations. Diabetes. 2015;64(3):766-774. https://doi.org/10.2337/db14-0685
Chen M, Woods SC, Porte D. Effect of Cerebral Intraventricular Insulin on Pancreatic Insulin Secretion in the Dog. Diabetes. 1975;24(10):910-914. https://doi.org/10.2337/diab.24.10.910
Filippi BM, Yang CS, Tang C, Lam TK. Insulin activates Erk1/2 signaling in the dorsal vagal complex to inhibit glucose production. Cell Metab. 2012;16(4):500-510. https://doi.org/10.1016/j.cmet.2012.09.005
Chaiken RL, Moses AC, Silver RD, et al. The Prolonged Hypoglycemic Effect Of An Insulin-Adjuvant Nasal Spray In Diabetes Is Secondary To Prolonged Suppression Of Hepatic Glucose Output. Clin Res. 1985;33(2):A426.
Shpakov AO, Moyseyuk IV, Chistyakova OV, et al. Treatment with intranasal insulin and serotonin restores the sensitivity of adenylyl cyclase to hormone in the brain of rats with long-term neonatal diabetes mellitus. Biulletenʹ FTSSKE im. V.A. Almazova. 2013;(1):21-27. (In Russ.)
Shpakov A, Chistyakova O, Derkach K, et al. Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes. Open Life Sci. 2012;7(1). https://doi.org/10.2478/s11535-011-0089-6
Shpakov AO, Derkach KV, Chistyakova OV, et al. Effect of intranasal insulin and serotonin on functional activity of the adenylyl cyclase system in myocardium, ovary, and uterus of rats with prolonged neonatal model of diabetes mellitus. Zh Evol Biokhim Fiziol. 2013;49(2):118-127. (In Russ.)
Sukhov IB, Derkach KV, Chistyakova OV, et al. Functional state of hypothalamic signaling systems in rats with type 2 diabetes mellitus treated with intranasal insulin. Zh Evol Biokhim Fiziol. 2016;52(3):184-194. (In Russ.)
Kuznetsova LA, Plesneva SA, Sharova TS, et al. Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of obese and type 2 diabetic rats as affected by the intranasal insulin treatment. Zh Evol Biokhim Fiziol. 2014;50(5):349-357. (In Russ.)
Kuznetsova LA, Sharova TS, Pertseva MN, Shpakov AO. Beta-adrenergic regulation of adenylyl cyclase signaling system in the myocardium and brain of rats with obesity and type 2 diabetes mellitus as affected by long-term intranasal insulin administration. Zh Evol Biokhim Fiziol. 2015;51(3):170-180. (In Russ.)
Shpakov AO, Chistyakova OV, Derkach KV, et al. Activity of receptor guanylyl cyclases in rats with neonatal streptozotocin diabetes and effect of intranasal administration of insulin and serotonin. Cell and Tissue Biology. 2011;53(7):591-599. (In Russ.)
Chistyakova OV, Sukhov IB, Shipilov VN, et al. Vliyanie intranazal’nogo vvedeniya insulina i serotonina na kognitivnye protsessy u krys s eksperimental’nym sakharnym diabetom 2-go tipa. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii. 2010;8(1):M75. (In Russ.)
Kuznetsova LA, Derkach KV, Sharova TS, et al. The activity of no-synthases in the brain, myocardium and skeletal muscles of obese rats and the influence of long-term treatment with intranasal insulin. Translational medicine. 2015;(1):39-45. (In Russ.)
Derkach KV, Ignat’eva PA, Shpakov AO. Hormonal regulation of adenylyl cyclase in the myocardium of male rats with metabolic syndrome and the influence of treatment with metformin and intranasally administered insulin. Translational medicine. 2016;3(1):73-81. (In Russ.) https://doi.org/10.18705/2311-4495-2016-3-1-73-81
Shpakov AO. Functional activity of the brain insulin signaling system in norm and in type 2 diabetes mellitus. Russian journal of physiology. 2015;101(10):1103-1127. (In Russ.)
Shpakov AO, Derkach KV. The Melanocortin Signal System of the Hypothalamus and Its Functional State in Type 2 Diabetes Mellitus and Metabolic Syndrome. Russian journal of physiology. 2017;103(5):504-517. (In Russ.)
Sukhov IB, Shipilov VN, Chistyakova OV, et al. Long-term intranasal insulin administration improves spatial memory in male rats with prolonged type 1 diabetes mellitus and in healthy rats. Dokl Akad Nauk. 2013;453(5):577. (In Russ.) https://doi.org/10.7868/S0869565213350272
Derkach KV, Bogush IV, Berstein LM, Shpakov AO. The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats. Horm Metab Res. 2015;47(12):916-924. https://doi.org/10.1055/s-0035-1547236

Close metadata