Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period
Derkach K.V.1 , Bondareva V.M.1, Shpakov A.O.2
1. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia 2. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia; Faculty of Medicine, Saint Petersburg State University, Saint-Petersburg, Russia
Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood are rare and contradictory. Approaches for the correction of metabolic and hormonal disorders caused by premature cessation of breastfeeding have not been developed yet. The aim of the work was to study the metabolic and hormonal parameters and changes in the hormonal status of the gonadal and thyroid systems in 10-month-old male rats with interruption of breastfeeding on days P19-P21, as well as to evaluate the restorative effect on them of four weeks of treatment with intranasal insulin (II) administered in the postnatal period (P28-P55) or in adulthood (P183-P210). Lactation interruption has been induced by treatment of lactating females with bromocriptine (10 mg/day/rat, P19-P21). Male rats with temporary cessation of breastfeeding developed characteristic signs of the metabolic syndrome (obesity, dyslipidemia, impaired glucose tolerance, hyperleptinemia), decreased levels of testosterone and thyroid hormones (fT4, tT3) and weakened the synthesis of testosterone and thyroxine, stimulated respectively by GnRH and thyroliberin. This was due to a decrease in the sensitivity of the testes to luteinizing hormone (LH) and the thyroid gland to thyroid-stimulating hormone (TSH). Treatment with II in early ontogenesis reduced body weight and fat, improved lipid profile, sensitivity to insulin, leptin, LH and TSH, restored the levels of testosterone and thyroid hormones and their stimulation by releasing factors. Treatment with II in adulthood normalized the levels of testosterone, thyroid hormones, their stimulation by releasing factors, but had a little effect on metabolic and hormonal parameters. The obtained data point to a wide range of metabolic and hormonal disorders in adult male rats with the “neonatal” model of metabolic syndrome and to the effectiveness of various strategies for their correction using long-term II treatment.
Derkach K.V., Bondareva V.M., Shpakov A.O. (2022) Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period. Biomeditsinskaya Khimiya, 68(4), 263-271.
Derkach K.V. et al. Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period // Biomeditsinskaya Khimiya. - 2022. - V. 68. -N 4. - P. 263-271.
Derkach K.V. et al., "Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period." Biomeditsinskaya Khimiya 68.4 (2022): 263-271.
Derkach, K. V., Bondareva, V. M., Shpakov, A. O. (2022). Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period. Biomeditsinskaya Khimiya, 68(4), 263-271.
References
Smith C.J., Ryckman K.K. (2015) Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes Metab. Syndr. Obes., 8, 295-302. CrossRef Scholar google search
Picó C., Reis F., Egas C., Mathias P., Matafome P. (2021) Lactation as a programming window for metabolic syndrome. Eur. J. Clin. Invest., 51(5), e13482. CrossRef Scholar google search
Lisboa P.C., Miranda R.A., Souza L.L., Moura E.G. (2021) Can breastfeeding affect the rest of our life? Neuropharmacology, 200, 108821. CrossRef Scholar google search
Badillo-Suárez P.A., Rodríguez-Cruz M., Nieves-Morales X. (2017) Impact of metabolic hormones secreted in human breast milk on nutritional programming in childhood obesity. J. Mammary Gland Biol. Neoplasia., 22(3), 171-191. CrossRef Scholar google search
Grote V., Verduci E., Scaglioni S., Vecchi F., Contarini G., Giovannini M., Koletzko B., Agostoni C. (2016) European childhood obesity project. Breast milk composition and infant nutrient intakes during the first 12 months of life. Eur. J. Clin. Nutr., 70(2), 250-256. CrossRef Scholar google search
Leghi G.E., Netting M.J., Lai C.T., Narayanan A., Dymock M., Rea A., Wlodek M.E., Geddes D.T., Muhlhausler B.S. (2021) Reduction in maternal energy intake during lactation decreased maternal body weight and concentrations of leptin, insulin and adiponectin in human milk without affecting milk production, milk macronutrient composition or infant growth. Nutrients, 13(6), 1892. CrossRef Scholar google search
Lima Nda S., de Moura E.G., Passos M.C., Nogueira Neto F.J., Reis A.M., de Oliveira E., Lisboa P.C. (2011) Early weaning causes undernutrition for a short period and programmes some metabolic syndrome components and leptin resistance in adult rat offspring. Br. J. Nutr., 105(9), 1405-1413. CrossRef Scholar google search
Francisco F.A., Barella L.F., Silveira S.D.S., Saavedra L.P.J., Prates K.V., Alves V.S., Franco C.C.D.S., Miranda R.A., Ribeiro T.A., Tófolo L.P., Malta A., Vieira E., Palma-Rigo K., Pavanello A., Martins I.P., Moreira V.M., de Oliveira J.C., Mathias P.C.F., Gomes R.M. (2018) Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood. Eur. J. Nutr., 57(2), 477-486. CrossRef Scholar google search
Ding X., Zhao Y., Zhu C.Y., Wu L.P., Wang Y., Peng Z.Y., Deji C., Zhao F.Y., Shi B.Y. (2021) The association between subclinical hypothyroidism and metabolic syndrome: An update meta-analysis of observational studies. Endocr. J., 68(9), 1043-1056. CrossRef Scholar google search
Louters M., Pearlman M., Solsrud E., Pearlman A. (2021) Functional hypogonadism among patients with obesity, diabetes, and metabolic syndrome. Int. J. Impot. Res., 2021, DOI: 10.1038/s41443-021-00496-7. CrossRef Scholar google search
Smith J.T., Spencer S.J. (2012) Preweaning over- and underfeeding alters onset of puberty in the rat without affecting kisspeptin. Biol. Reprod., 86(5), 145, 1-8. CrossRef Scholar google search
Ayala-Moreno R., Racotta R., Anguiano B., Aceves C., Quevedo L. (2013) Perinatal undernutrition programmes thyroid function in the adult rat offspring. Br. J. Nutr., 110(12), 2207-2215. CrossRef Scholar google search
Pietrobon C.B., Bertasso I.M., Silva B.S., Peixoto-Silva N., Oliveira E., Moura E.G., Lisboa P.C. (2020) Body adiposity and endocrine profile of female Wistar rats of distinct ages that were early weaned. Horm. Metab. Res., 52(1), 58-66. CrossRef Scholar google search
Souza L.L., de Moura E.G., Lisboa P.C. (2020) Does early weaning shape future endocrine and metabolic disorders? Lessons from animal models. J. Dev. Orig. Health Dis., 11(5), 441-451. CrossRef Scholar google search
Shpakov A.O., Derkach K.V., Berstein L.M. (2015) Brain signaling systems in the Type 2 diabetes and metabolic syndrome: Promising target to treat and prevent these diseases. Future Sci. OA, 1(3), FSO25. CrossRef Scholar google search
Scherer T., Sakamoto K., Buettner C. (2021) Brain insulin signalling in metabolic homeostasis and disease. Nat. Rev. Endocrinol., 17(8), 468-483. CrossRef Scholar google search
Hu S.H., Jiang T., Yang S.S., Yang Y. (2013) Pioglitazone ameliorates intracerebral insulin resistance and tau-protein hyperphosphorylation in rats with type 2 diabetes. Exp. Clin. Endocrinol. Diabetes, 121(4), 220-224. CrossRef Scholar google search
Derkach K., Zakharova I., Zorina I., Bakhtyukov A., Romanova I., Bayunova L., Shpakov A. (2019) The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect. PLoS One, 14(3), e0213779. CrossRef Scholar google search
Derkach K.V., Bakhtyukov A.A., Romanova I.V., Zorina I.I., Bayunova L.V., Bondareva V.M., Morina I.Yu., Kumar Roy V., Shpakov A.O. (2020) The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus. Andrologia, 52(11), e13816. CrossRef Scholar google search
Derkach K.V., Bogush I.V., Berstein L.M., Shpakov A.O. (2015) The influence of intranasal insulin on hypothalamicpituitary- thyroid axis in normal and diabetic rats. Horm. Metab. Res., 47(12), 916-924. CrossRef Scholar google search
Strazzullo P., Barbato A., Siani A., Cappuccio F.P., Versiero M., Schiattarella P., Russo O., Avallone S., della Valle E., Farinaro E. (2008) Diagnostic criteria for metabolic syndrome: A comparative analysis in an unselected sample of adult male population. Metabolism, 57(3), 355-361. CrossRef Scholar google search
Henderson G.C. (2021) Plasma free fatty acid concentration as a modifiable risk factor for metabolic disease. Nutrients, 13(8), 2590. CrossRef Scholar google search
Lima Nda S., Franco J.G., Peixoto-Silva N., Maia L.A., Kaezer A., Felzenszwalb I., de Oliveira E., de Moura E.G., Lisboa P.C. (2014) Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning. Eur. J. Nutr., 53(1), 73-82. CrossRef Scholar google search
Pietrobon C.B., Miranda R.A., Bertasso I.M., Mathias P.C.F., Bonfleur M.L., Balbo S.L., Reis M.A.B., Latorraca M.Q., Arantes V.C., de Oliveira E., Lisboa P.C., de Moura E.G. (2020) Early weaning induces short- and long-term effects on pancreatic islets in Wistar rats of both sexes. J. Physiol., 598(3), 489-502. CrossRef Scholar google search
Huang P.L. (2009) A comprehensive definition for metabolic syndrome. Dis. Model. Mech., 2(5-6), 231-237. CrossRef Scholar google search
Virgen-Carrillo C.A., de Los Ríos D.L.H., Torres K.R., Moreno A.G.M. (2021) Diagnostic criteria for metabolic syndrome in diet-induced rodent models: A systematic review. Curr. Diabetes Rev., 17(8), e140421192834. CrossRef Scholar google search
Derkach K.V., Ivantsov A.O., Chistyakova O.V., Sukhov I.B., Buzanakov D.M., Kulikova A.A., Shpakov A.O. (2017) Intranasal insulin restores metabolic parameters and insulin sensitivity in rats with metabolic syndrome. Bull. Exp. Biol. Med., 163(2), 184-189. CrossRef Scholar google search
Benedict C., Brede S., Schiöth H.B., Lehnert H., Schultes B., Born J., Hallschmid M. (2011) Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men. Diabetes, 60(1), 114-118. CrossRef Scholar google search
Ott V., Lehnert H., Staub J., Wönne K., Born J., Hallschmid M. (2015) Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia. Diabetes, 64(3), 760-765. CrossRef Scholar google search
Derkach K.V., Bondareva V.M., Shpakov A.O. (2019) Regulatory effects of intranasal C-peptide and insulin on thyroid and androgenic status of male rats with moderate type 1 diabetes mellitus. J. Evol. Biochem. Physiol., 55(6), 493-496. CrossRef Scholar google search
