Therapeutical Potential of T3 as Adjuvant Therapy in Male Alloxan-induced Diabetic Rats

Abstract Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in contr...

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Published in:	Endocrinology (Philadelphia) Vol. 165; no. 7
Main Authors:	Florido Neto, Armando Ribeiro, Agostini, Lucas, Silva Jr, Luciano Pedro da, Nunes, Maria Tereza
Format:	Journal Article
Language:	English
Published:	US Oxford University Press 27-05-2024
Subjects:	Adipose tissue Alloxan Animal models Animals Blood glucose Blood Glucose - drug effects Blood Glucose - metabolism Cytokines Cytokines - metabolism Decay rate Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Disease management Effectiveness Fasting Glucose Transporter Type 4 - metabolism Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Hypothyroidism Immunoblotting Inflammation Insulin Insulin Resistance Male Males Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscles NF-kappa B - metabolism NF-κB protein Parameters Rats Rats, Wistar Skeletal muscle Thyroid Thyroid gland Thyroid hormones Thyroid-stimulating hormone Thyrotropin - blood Triiodothyronine Triiodothyronine - blood Triiodothyronine - pharmacology cytokines diabetes mellitus insulin hypothyroidism insulin resistance triiodothyronine
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Summary:	Abstract Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g−1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1945-7170 0013-7227 1945-7170
DOI:	10.1210/endocr/bqae066