Horm Metab Res 2014; 46(10): 710-716
DOI: 10.1055/s-0034-1370962
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Thyroidectomy and Propylthiouracil-Induced Hypothyroidism on Insulin Secretion in Male Rats

A. Godini
1   Department of Physiology, Faculty of Medicine, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
A. Ghasemi
2   Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3   Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
N. Karbalaei
1   Department of Physiology, Faculty of Medicine, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
S. Zahediasl
2   Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3   Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
› Author Affiliations
Further Information

Publication History

received 22 October 2013

accepted 12 February 2014

Publication Date:
13 March 2014 (online)

Abstract

Data available on thyroid dysfunction and insulin secretion are inconsistent. The aim of this study was to assess the effect of hypothyroidism on insulin secretion, in vivo and in vitro, in rats. Adult Wistar male rats were divided into 4 groups, the control, the propylthiouracyl (PTU)-treated hypothyroid, the surgically thyroidectomized, and the sham-operated thyroidectomized. After 5 weeks, intravenous glucose tolerance test (IVGTT) was performed and 3 weeks later pancreatic islets were isolated to assess glucose induced insulin secretion and insulin content. Fasting serum glucose and insulin levels did not differ between the groups, but serum glucose concentration during IVGTT in the PTU-induced hypothyroid group was significantly higher as compared to controls, throughout 5–60 min. The serum glucose concentration during IVGTT in the thyroidectomized rats was also significantly higher than in the sham-operated ones, except at 10 and 60 min. The area under the curve of the serum insulin was significantly lower during IVGTT in the PTU-treated (10 010±1 380 pmol/l/60 min) and thyroidectomized (13 930±2 786) groups vs. their comparable groups (19 150±2 110), p<0.01 and (20 650±1 601), p<0.05, respectively. In the PTU-treated, but not in thyroidectomized animals, insulin secretion in response to glucose 8.3 and 16.7 mM was significantly lower than their comparable group. The results show that PTU- and thyroidectomy-induced hypothyroidism leads to impaired glucose tolerance due to reduced glucose stimulated insulin secretion. Islets insulin secretion is positively correlated with serum T3 and T4 concentrations.

 
  • References

  • 1 Chen G, Wu J, Lin Y, Huang B, Yao J, Jiang Q, Wen J, Lin L. Associations between cardiovascular risk, insulin resistance, beta-cell function and thyroid dysfunction: a cross-sectional study in She ethnic minority group of Fujian Province in China. Eur J Endocrinol 2010; 163: 775-782
  • 2 Zhurova MV, Lugovaia NA. Carbohydrate tolerance and islet apparatus function in patients with different forms of hypothyroidism. Probl Endokrinol (Mosk) 1983; 29: 36-40
  • 3 Handisurya A, Pacini G, Tura A, Gessl A, Kautzky-Willer A. Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin Endocrinol (Oxf) 2008; 69: 963-969
  • 4 Achmadi J, Terashima Y. The effect of propylthiouracyl-induced low thyroid function on secretion response and action of insulin in sheep. Domest Anim Endocrinol 1995; 12: 157-166
  • 5 Hofer-Inteeworn N, Panciera DL, Monroe WE, Saker KE, Davies RH, Refsal KR, Kemnitz JW. Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs. Am J Vet Res 2012; 73: 529-538
  • 6 Poltorak VV, Iurchenko MZ, Ladogubets EV. Effect of thyroidectomy on the beta-cell function of the pancreatic islet apparatus. Probl Endokrinol (Mosk) 1984; 30: 76-81
  • 7 Lenzen S, Joost HG, Hasselblatt A. Thyroid function and insulin secretion from the perfused pancreas in the rat. Endocrinology 1976; 99: 125-129
  • 8 Lenzen S, Bailey CJ. Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr Rev 1984; 5: 411-434
  • 9 Diaz GB, Paladini AA, Garcia ME, Gagliardino JJ. Changes induced by hypothyroidism in insulin secretion and in the properties of islet plasma membranes. Arch Int Physiol Biochim Biophys 1993; 101: 263-269
  • 10 Gomez Dumm CL, Garcia ME, Borelli MI, Cortizo AM, De Gagliardino EE, Gagliardino JJ. Effect of the removal of different endocrine glands upon insulin secretion and B-cell ultrastructure. Acta Anat (Basel) 1984; 119: 241-247
  • 11 Cortizo AM, Gomez Dumm CL, Gagliardino JJ. Effect of thyroid hormone levels upon pancreatic islet function. Acta Physiol Pharmacol Latinoam 1985; 35: 181-191
  • 12 Sener A, Malaisse-Lagae F, Gervy-Decoster C, Malaisse WJ. Enzymatic, metabolic and secretory perturbations in pancreatic islets of thyroidectomized rats. Cell Biochem Funct 1993; 11: 145-151
  • 13 Karbalaei N, Ghasemi A, Faraji F, Zahediasl S. Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats. Scand J Clin Lab Invest 2013; 73: 87-94
  • 14 Vranckx R, Rouaze-Romet M, Savu L, Mechighel P, Maya M, Nunez EA. Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone. J Endocrinol 1994; 142: 77-84
  • 15 Maran RR, Senthilkumaran B, Udhayakumar RC, Arunakaran J, Aruldhas MM. Thyroidectomy modulates rat prostatic monosaccharides. Int J Androl 2000; 23: 156-162
  • 16 Farahani H, Ghasemi A, Roghani M, Zahediasl S. The effect of maternal hypothyroidism on the carbohydrate metabolism and insulin secretion of isolated islets in adult male offspring of rats. Horm Metab Res 2010; 42: 792-797
  • 17 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 18 Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 1967; 16: 35-39
  • 19 Welsh N, Sjoholm A. Polyamines and insulin production in isolated mouse pancreatic islets. Biochem J 1988; 252: 701-707
  • 20 Awouters P, Meissner HP, Henquin JC. Thyrotropin-releasing hormone and insulin release: in vitro studies with islets of normal and dysthyroid mice. Diabetes Res 1985; 2: 105-110
  • 21 Doong ML, Wang JW, Chung SC, Liu JY, Hwang C, Hwang CY, Day CH, Liu YF, Young TK, Ho LL, Wang PS. Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory polypeptide in male rats. Metabolism 1997; 46: 154-158
  • 22 Tonooka N, Kobayashi S. Effect of propylthiouracil on nycthemeral and sex related variation of plasma TSH in rats. Endocrinol Jpn 1980; 27: 27-32
  • 23 Kahn CR. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 1994; 43: 1066-1084
  • 24 Dimitriadis GD, Leighton B, Parry-Billings M, West D, Newsholme EA. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J 1989; 257: 369-373
  • 25 Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Panagiotakos DB, Koukkou E, Tzanela M, Thalassinos N, Raptis SA. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab 2006; 91: 4930-4937
  • 26 Kosovskii MI, Katkova SP, Nugmanova LB, Ismailov SI, Kasymov UA. Glucose tolerance disorders in patients with hypothyroidism. Probl Endokrinol (Mosk) 1992; 38: 26-29
  • 27 Rochon C, Tauveron I, Dejax C, Benoit P, Capitan P, Fabricio A, Berry C, Champredon C, Thieblot P, Grizard J. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond) 2003; 104: 7-15
  • 28 Brenta G, Celi FS, Pisarev M, Schnitman M, Sinay I, Arias P. Acute thyroid hormone withdrawal in athyreotic patients results in a state of insulin resistance. Thyroid 2009; 19: 665-669
  • 29 Havekes B, Sauerwein HP. Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?. Curr Opin Clin Nutr Metab Care 2010; 13: 641-646
  • 30 Cettour-Rose P, Theander-Carrillo C, Asensio C, Klein M, Visser TJ, Burger AG, Meier CA, Rohner-Jeanrenaud F. Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 2005; 48: 624-633
  • 31 Stanicka S, Vondra K, Pelikanova T, Vlcek P, Hill M, Zamrazil V. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med 2005; 43: 715-720
  • 32 Owecki M, Nikisch E, Sowinski J. Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally thyroidectomized patients. Acta Clin Belg 2006; 61: 69-73
  • 33 Dariyerli N, Andican G, Catakoglu AB, Hatemi H, Burcak G. Hyperuricemia in hypothyroidism: is it associated with post-insulin infusion glycemic response?. Tohoku J Exp Med 2003; 199: 59-68
  • 34 Arikan S, Bahceci M, Tuzcu A, Celik F, Gokalp D. Postprandial hyperlipidemia in overt and subclinical hypothyroidism. Eur J Intern Med 2012; 23: e141-e145
  • 35 Nada AM. Effect of treatment of overt hypothyroidism on insulin resistance. World J Diabetes 2013; 4: 157-161
  • 36 Matthaei S, Trost B, Hamann A, Kausch C, Benecke H, Greten H, Hoppner W, Klein HH. Effect of in vivo thyroid hormone status on insulin signalling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes. J Endocrinol 1995; 144: 347-357
  • 37 Shah JH, Motto GS, Papagiannes E, Williams GA. Insulin metabolism in hypothyroidism. Diabetes 1975; 24: 922-925
  • 38 Michael UF, Kelley J, Vaamonde CA. Impaired renal bicarbonate reabsorption in the hypothyroid rat. Am J Physiol 1979; 236: F536-F540
  • 39 Michael UF, Kelley J, Meeks LA, Vaamonde CA. Renal acidification in the hypothyroid rat. Evaluation by urinary CO2 tension. Can J Physiol Pharmacol 1981; 59: 273-280
  • 40 Potenza M, Via MA, Yanagisawa RT. Excess thyroid hormone and carbohydrate metabolism. Endocr Pract 2009; 15: 254-262
  • 41 Dipippo VA, Powers CA. Tamoxifen and ICI 182,780 interactions with thyroid hormone in the ovariectomized-thyroidectomized rat. J Pharmacol Exp Ther 1997; 281: 142-148