Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000025.xml
Download PDF
Horm Metab Res 2015; 47(12): 916-924
DOI: 10.1055/s-0035-1547236
DOI: 10.1055/s-0035-1547236
Endocrine Research
The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats
Authors
Further Information
Publication History
received 02 December 2014
accepted 11 February 2015
Publication Date:
06 March 2015 (online)
Abstract
The functions of hypothalamic-pituitary-thyroid axis are attenuated in type 1 diabetes mellitus due to insulin deficiency. The use of intranasally administered insulin is of considerable interest for treatment of diabetes and cognitive disorders, but its effect on the thyroid system has not been investigated yet. We studied the influence of long-term treatment with intranasal insulin on the hypothalamic-pituitary-thyroid axis of nondiabetic rats and diabetic animals with streptozotocin models of acute and mild type 1 diabetes mellitus. This treatment was carried out for 28 days in acute (daily does of 0.3, 0.6, and 1.5 IU of insulin per rat) and for 135 days in mild diabetes (daily dose of 0.45 IU/rat). Nondiabetic rats were treated in a similar manner. Intranasal insulin in both models of diabetes resulted in the improvement of thyroid status; manifested as increase of thyroid hormones levels and restoration of response to thyroliberin. In acute diabetes, a daily dose of 0.6 IU/rat was the most effective. Twenty eight days treatment of nondiabetic rats with intranasal insulin at a dose of 0.3 IU/rat resulted in a significant increase of free and total thyroxine levels. Longer treatment of rats with mild diabetes and nondiabetic animals significantly increased thyrotropin level. Thus, long-term intranasal insulin treatment restored the hypothalamic-pituitary-thyroid axis function in type 1 diabetes, but led to a significant increase in the thyrotropin level, which must be considered when designing a strategy for the use of intranasal insulin in clinical applications.
Supporting Information
- for this article is available online at http://www.thieme-connect.de/products
- Supporting Information (PDF) (opens in new window)
-
References
- 1 Zoeller RT, Tan SW, Tyl RW. General background on the hypothalamic-pituitary-thyroid (HPT) axis. Crit Rev Toxicol 2007; 37: 11-53
- 2 Chakrabarti S. Thyroid functions and bipolar affective disorder. J Thyroid Res 2011; 2011 Article ID 306367, 13 Pages
- 3 Ertek S, Cicero AF. Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology. Arch Med Sci 2013; 9: 944-952
- 4 Sharma AK, Arya R, Mehta R, Sharma R, Sharma AK. Hypothyroidism and cardiovascular disease: factors, mechanism and future perspectives. Curr Med Chem 2013; 20: 4411-4418
- 5 Wood-Allum CA, Shaw PJ. Thyroid disease and the nervous system. In: Aminoff M, Boller F, Swaab D. (eds.) Handbook of Clinical Neurology. Amsterdam: Elsevier; 2014. 120. 703-735
- 6 Dittmar M, Kahaly GJ. Genetics of the autoimmune polyglandular syndrome type 3 variant. Thyroid 2010; 20: 737-743
- 7 Kadiyala R, Peter R, Okosieme OE. Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract 2010; 64: 1130-1139
- 8 Duntas LH, Orgiazzi J, Brabant G. The Interface between thyroid and diabetes mellitus. Clin Endocrinol (Oxf) 2011; 75: 1-9
- 9 Gray RS, Borsey DQ, Seth J, Herd R, Brown NS, Clarke BF. Prevalence of subclinical thyroid failure in insulin-dependent diabetes. J Clin Endocrinol Metab 1980; 50: 1034-1037
- 10 Mouradian M, Abourizk N. Diabetes mellitus and thyroid disease. Diabetes Care 1983; 6: 512-520
- 11 Wilber JF, Banerji A, Prasad C, Mori M. Alterations in hypothalamic-pituitary-thyroid regulation produced by diabetes mellitus. Life Sci 1981; 28: 1757-1763
- 12 Bestetti GE, Reymond MJ, Perrin IV, Kniel PC, Lemarchand-Béraud T, Rossi GL. Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands. Virchows Arch B Cell Pathol Incl Mol Pathol 1987; 53: 69-78
- 13 Rondeel JM, de Greef WJ, Heide R, Visser TJ. Hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes. Endocrinology 1992; 130: 216-220
- 14 van der Elst JPS, van der Heide D. Effects of streptozotocin-induced diabetes and food restriction on quantities and source of T4 and T3 in rat tissues. Diabetes 1992; 41: 147-152
- 15 Nascimento-Saba CC, Breitenbach MM, Rosenthal D. Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus. Braz J Med Biol Res 1997; 30: 269-274
- 16 Shpakov A, Derkach K, Moyseyuk I, Chistyakova O. Alterations of hormone-sensitive adenylyl cyclase system in the tissues of rats with long-term streptozotocin diabetes and the influence of intranasal insulin. Dataset Papers Pharmacol 2013; 2013: 698435 http://dx.doi.org/10.7167/2013/698435
- 17 Shpakov AO, Derkach KV, Chistyakova OV, Moyseyk IV, Bondareva VM. The effect of long-term diabetes mellitus induced by treatment with streptozotocin in 6-week-old rats on functional activity of the adenylyl cyclase system. Cell Tis Biol 2014; 8: 68-79
- 18 Derkach K, Moyseyuk IV, Shpakov AO. The influence of prolonged streptozotocin diabetes on the thyroid gland function in rats. Dokl Biochem Biophys 2013; 451: 217-220
- 19 Freiherr J, Hallschmid M, Frey 2nd WH, Brünner YF, Chapman CD, Hölscher C, Craft S, De Felice FG, Benedict C. Intranasal insulin as a treatment for Alzheimer’s disease: a review of basic research and clinical evidence. CNS Drugs 2013; 27: 505-514
- 20 McIntyre RS, Soczynska JK, Woldeyohannes HO, Miranda A, Vaccarino A, Macqueen G, Lewis GF, Kennedy SH. A randomized, double-blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder. Bipolar Disord 2012; 14: 697-706
- 21 Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol (Lausanne) 2014; 5: 161
- 22 Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab 2008; 93: 1339-1344
- 23 Ott V, Benedict C, Schultes B, Born J, Hallschmid M. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism. Diabetes Obes Metab 2012; 14: 214-221
- 24 Shpakov AO, Chistyakova OV, Derkach KV, Moiseyuk IV, Bondareva VM. Intranasal insulin affects adenylyl cyclase system in rat tissues in neonatal diabetes. Central Eur J Biol 2012; 7: 33-47
- 25 Saravanan G, Ponmurugan P. Antidiabetic effect of S-allylcysteine: effect on thyroid hormone and circulatory antioxidant system in experimental diabetic rats. J Diabetes Complicat 2012; 26: 280-285
- 26 Steger RW, Rabe MB. The effect of diabetes mellitus on endocrine and reproductive function. Proc Soc Exp Biol Med 1997; 214: 1-11
- 27 Lin CH, Lee YJ, Huang CY, Kao HA, Shih BF, Wang AM, Lo FS. Thyroid function in children with newly diagnosed type 1 diabetes mellitus. Acta Paediatr Taiwan 2003; 44: 145-149
- 28 Bestetti GE, Brändli P, Rossi GL. Secretory disorders in pituitary thyrotropes of streptozocin-diabetic male rats. Acta Anat (Basel) 1994; 149: 215-220
- 29 Rodríguez M, Rodríguez F, Jolin T, Santisteban P. Comparative effects of food restriction, fasting, diabetes and thyroidectomy on growth hormone and thyrotropin gene expression in the rat pituitary. Eur J Endocrinol 1995; 133: 110-116
- 30 Ortiga-Carvalho TM, Curty FH, Nascimento-Saba CC, Moura EG, Polak J, Pazos-Moura CC. Pituitary neuromedin B content in experimental fasting and diabetes mellitus and correlation with thyrotropin secretion. Metabolism 1997; 46: 149-153
- 31 Aláez C, Calvo R, Obregón MJ, Alvarez C, Goya L, Escrivá F, Martín MA, Pascual-Leone AM. Influence of type II 5′ deiodinase on TSH content in diabetic rats. J Physiol Biochem 2001; 57: 221-230
- 32 Liu C, Shu C. Morphological studies of the adrenal zona glomerulosa cells and the thyroid and pituitary glands in streptozocin-induced experimental diabetic rats. Zhonghua Bing Li Xue Za Zhi 1996; 25: 358-360
- 33 Nascimento-Saba CC, Brito AC, Pereira MJ, Carvalho JJ, Rosenthal D. Autoradiographic thyroid evaluation in short-term experimental diabetes mellitus. Braz J Med Biol Res 1998; 31: 299-302
- 34 Moiseyuk IV, Derkach KV, Shpakov AO. Functional activity of thyroid gland in male rats with acute and mild streptozotocin diabetes. J Evol Biochem Physiol 2014; 50: 310-320
- 35 Chase HP, Garg SK, Cockerham RS, Wilcox WD, Walravens PA. Thyroid hormone replacement and growth of children with subclinical hypothyroidism and diabetes. Diabet Med 1990; 7: 299-303
- 36 Ortiz-Caro J, González C, Jolin T. Diurnal variations of plasma growth hormone, thyrotropin, thyroxine, and triiodothyronine in streptozotocin-diabetic and food-restricted rats. Endocrinology 1984; 115: 2227-2232
- 37 Katovich MJ, Marks KS, Sninsky CA. Effect of insulin on the altered thyroid function and adrenergic responsiveness in the diabetic rat. Can J Physiol Pharmacol 1993; 71: 568-575
- 38 Santos MC, Louzada RA, Souza EC, Fortunato RS, Vasconcelos AL, Souza KL, Castro JP, Carvalho DP, Ferreira AC. Diabetes mellitus increases reactive oxygen species production in the thyroid of male rats. Endocrinology 2013; 154: 1361-1372
- 39 van Haasteren GA, Sleddens-Linkels E, van Toor H, Klootwijk W, de Jong FH, Visser TJ, de Greef WJ. Possible role of corticosterone in the down-regulation of the hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes mellitus in rats. J Endocrinol 1997; 153: 259-267
- 40 McCarty MF. Central insulin may up-regulate thyroid activity by suppressing neuropeptide Y release in the paraventricular nucleus. Med Hypotheses 1995; 45: 193-199
- 41 Fekete C, Kelly J, Mihaly E, Sarkar S, Rand WM, Legradi G, Emerson CH, Lechan RM. Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis. Endocrinology 2001; 142: 2606-2613
- 42 Wang J, Leibowitz KL. Central insulin inhibits hypothalamic galanin and neuropeptide Y gene expression and peptide release in intact rats. Brain Res 1997; 777: 231-236
- 43 Nillni EA. Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs. Front Neuroendocrinol 2010; 31: 134-156
- 44 Skamene A, Patel YC. Infusion of graded concentrations of somatostatin in man: pharmacokinetics and differential inhibitory effects on pituitary and islet hormones. Clin Endocrinol (Oxf) 1984; 20: 555-564
- 45 Grimberg A. Somatostatin and cancer: applying endocrinology to oncology. Cancer Biol Ther 2004; 3: 731-733
- 46 Matsushima Y, Makino H, Kanatsuka A, Osegawa M, Kumagai A, Nishimura M, Tochino Y, Makino S. Pancreatic somatostatin contents in spontaneously diabetic KK and non-obese diabetic (NOD) mice. Horm Metab Res 1982; 14: 292-298
- 47 Orskov H, Flyvbjerg A, Frystyk J, Ledet T, Møller N, Christensen SE, Harris AG. Octreotide and diabetes: theoretical and experimental aspects. Metabolism 1992; 41: 66-71
- 48 El-Salhy M, Spångéus A. Gastric emptying in animal models of human diabetes: correlation to blood glucose level and gut neuroendocrine peptide content. Ups J Med Sci 2002; 107: 89-99
- 49 Fernstrom JD, Fernstrom MH, Kwok RP. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus. Am J Physiol 1990; 258: 661-666
- 50 Tang F, Wong RP. Pituitary contents of β-endorphin, dynorphin, substance P, cholecystokinin and somatostatin in rats with streptozotocin-induced diabetes. Biol Signals 1996; 5: 44-50
- 51 Szilvássy Z, Németh J, Kovács P, Paragh G, Sári R, Vígh L, Peitl B. Insulin resistance occurs in parallel with sensory neuropathy in streptozotocin-induced diabetes in rats: differential response to early vs late insulin supplementation. Metabolism 2012; 61: 776-786
- 52 Caruso MA, Sheridan MA. Differential regulation of the multiple insulin and insulin receptor mRNAs by somatostatin. Mol Cell Endocrinol 2014; 384: 126-133
- 53 Ciaccio C, Tundo GR, Grasso G, Spoto G, Marasco D, Ruvo M, Gioia M, Rizzarelli E, Coletta M. Somatostatin: a novel substrate and a modulator of insulin-degrading enzyme activity. J Mol Biol 2009; 385: 1556-1567
- 54 Fekete C, Singru PS, Sanchez E, Sarkar S, Christoffolete MA, Riberio RS, Rand WM, Emerson CH, Bianco AC, Lechan RM. Differential effects of central leptin, insulin, or glucose administration during fasting on the hypothalamic-pituitary-thyroid axis and feeding-related neurons in the arcuate nucleus. Endocrinology 2006; 147: 520-529
- 55 Alagiakrishnan K, Sankaralingam S, Ghosh M, Mereu L, Senior P. Antidiabetic drugs and their potential role in treating mild cognitive impairment and Alzheimer’s disease. Discov Med 2013; 16: 277-286