Derkach K V, Bogush I V, Berstein L M, Shpakov A O
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Laboratory of Oncoendocrinology; N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia.
Horm Metab Res. 2015 Nov;47(12):916-24. doi: 10.1055/s-0035-1547236. Epub 2015 Mar 6.
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.
在1型糖尿病中，由于胰岛素缺乏，下丘脑 - 垂体 - 甲状腺轴的功能会减弱。经鼻给予胰岛素对于糖尿病和认知障碍的治疗具有重要意义，但其对甲状腺系统的影响尚未得到研究。我们研究了长期经鼻给予胰岛素对非糖尿病大鼠以及链脲佐菌素诱导的急性和轻度1型糖尿病模型的糖尿病动物下丘脑 - 垂体 - 甲状腺轴的影响。急性模型中（每只大鼠每日剂量为0.3、0.6和1.5国际单位胰岛素），这种治疗持续28天；轻度糖尿病模型中（每日剂量为0.45国际单位/大鼠），治疗持续135天。非糖尿病大鼠也采用类似方式治疗。在两种糖尿病模型中，经鼻给予胰岛素均能改善甲状腺状态，表现为甲状腺激素水平升高以及对促甲状腺激素释放激素反应的恢复。在急性糖尿病模型中，每日剂量为0.6国际单位/大鼠最为有效。以0.3国际单位/大鼠的剂量经鼻给予胰岛素对非糖尿病大鼠进行28天治疗后，游离甲状腺素和总甲状腺素水平显著升高。对轻度糖尿病大鼠和非糖尿病动物进行更长时间的治疗会显著提高促甲状腺激素水平。因此，长期经鼻给予胰岛素治疗可恢复1型糖尿病中下丘脑 - 垂体 - 甲状腺轴的功能，但会导致促甲状腺激素水平显著升高，在设计临床应用中经鼻胰岛素的使用策略时必须考虑这一点。
