The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

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.

Jinlida Granules Improve Dysfunction of Hypothalamic-Pituitary-Thyroid Axis in Diabetic Rats Induced by STZ

“…Our results showed significantly lower T3 and T4 levels in diabetic group than those in NC group, which was consistent with previous results [ 18 – 21 ]. We also detected no significant difference on the levels of TSH and pro-TRH mRNA between normal and DM group, which were in line with results of Nascimento-Saba et al [ 20 ] and Derkach et al [ 22 ]. However, Akbarzadeh et al detected that TSH in diabetic rats induced by 55 mg/kg STZ was even higher than that of NC group [ 18 ], and similar result was proved in other studies using low-dose STZ (30–40 mg/kg) to induce mild diabetic model [ 22 , 23 ].…”

“…We also detected no significant difference on the levels of TSH and pro-TRH mRNA between normal and DM group, which were in line with results of Nascimento-Saba et al [ 20 ] and Derkach et al [ 22 ]. However, Akbarzadeh et al detected that TSH in diabetic rats induced by 55 mg/kg STZ was even higher than that of NC group [ 18 ], and similar result was proved in other studies using low-dose STZ (30–40 mg/kg) to induce mild diabetic model [ 22 , 23 ]. The discrepancies might be related to the dose and manner of STZ administration in diabetes model.…”

Comparative Study of the Steroidogenic Effects of Human Chorionic Gonadotropin and Thieno[2,3-D]pyrimidine-Based Allosteric Agonist of Luteinizing Hormone Receptor in Young Adult, Aging and Diabetic Male Rats

“…Since the structure of the allosteric site of LHCGR is similar to that of thyroid stimulating hormone receptor (TSHR), we studied the effect of TP4/2 on the AC activity in the rat thyroidal membranes in in vitro conditions and on the baseline and thyrotropin-releasing hormone (TRH)-stimulated blood levels of thyroid hormones in young adult rats in in vivo conditions. In the in vivo experiments, TRH was administered intranasally (300 μg/kg), as previously described [ 42 ].…”

The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities

“…In recent years, the interest in insulin function in the central nervous system is very high. Insulin’s action on hypothalamic neurons was shown to regulate energetic metabolism and the function of endocrine systems due to the production of hypothalamic releasing factors by these neurons [20,26]. Administration of insulin to animals or humans suffering from neurodegenerative or diabetic diseases was shown to ameliorate the cognitive functions and to increase the viability of brain neurons [4,5,6,27,28].…”