Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1980 September; 66(3): 574–582.
PMCID: PMC371686

Effect of Thyroid Status on Insulin Action in Rat Adipocytes and Skeletal Muscle


Isolated adipocytes and soleus muscles prepared from mature rats, rendered hypothyroid by a low iodine diet and propylthiouracil, markedly resisted the ability of insulin to increase glucose utilization. In adipocytes, the sum of basal d-(1-14C)-glucose conversion to CO2, glyceride-glycerol, and fatty acid was unaltered by hypothyroidism, although conversion to fatty acid was decreased. The response of each of these metabolic pathways to insulin at all concentrations tested was greatly diminished in hypothyroid rat adipocytes. 3-O-Methylglucose transport rates in the presence of insulin were not significantly different in adipocytes from hypothyroid as compared with euthyroid rats, although basal transport rates were significantly higher in the hypothyroid state. Lipolysis and cyclic AMP accumulation in adipocytes from hypothyroid rats in response to theophylline were markedly diminished compared with euthyroid controls, but insulin was about as effective in inhibiting lipolysis in these cells as in those derived from euthyroid animals. The binding of 125I-insulin to adipocytes at several hormone concentrations was also shown to be unaffected by hypothyroidism.

In soleus muscle, basal glucose conversion to H2O and glycogen was unaltered in the hypothyroid state, whereas insulin action on these pathways was markedly inhibited. The decrease in muscle insulin responsiveness was less marked than that observed in adipocytes. Uptake of either 2-deoxyglucose or l-arabinose in the presence or absence of insulin was similar in soleus muscles derived from euthryoid vs. hypothyroid rats. Similarly, insulin action on the conversion of soleus muscle glycogen synthase D to the I form in the absence of glucose was unaltered by hypothyroidism. We conclude that (a) hypothyroidism in mature rats leads to a marked decrease in the responsiveness of glucose metabolism in adipocytes and skeletal muscle to insulin; (b) no detectable impairment of the membrane insulin effector systems that mediate the regulation of adipocyte hexose transport and glycogen synthase is caused by hypothyroidism in this animal model; and (c) the cellular defect that leads to apparent insulin resistance of adipocyte and soleus muscle glucose utilization resides at the level of one or more intracellular enzymes involved in glucose catabolism.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Danforth E, Jr, Burger AG, Wimpfheimer C. Nutritionally-induced alterations in thyroid hormone metabolism and thermogenesis. Experientia Suppl. 1978;32:213–217. [PubMed]
  • Wimpfheimer C, Saville E, Voirol MJ, Danforth E, Jr, Burger AG. Starvation-induced decreased sensitivity of resting metabolic rate to triiodothyronine. Science. 1979 Sep 21;205(4412):1272–1273. [PubMed]
  • Goswami A, Rosenberg IN. Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium. Endocrinology. 1978 Dec;103(6):2223–2233. [PubMed]
  • Armstrong KJ, Stouffer JE, Van Inwegen RG, Thompson WJ, Robison GA. Effects of thyroid hormone deficiency on cyclic adenosine 3':5'-monophosphate and control of lipolysis in fat cells. J Biol Chem. 1974 Jul 10;249(13):4226–4231. [PubMed]
  • Gliemann J. Insulin-like activity of dilute human serum assayed by an isolated adipose cell method. Diabetes. 1965 Oct;14(10):643–649. [PubMed]
  • Gilman AG. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. [PubMed]
  • Brown BL, Albano JD, Ekins RP, Sgherzi AM. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. [PubMed]
  • Fain JN, Reed N, Saperstein R. The isolation and metabolism of brown fat cells. J Biol Chem. 1967 Apr 25;242(8):1887–1894. [PubMed]
  • Le Marchand-Brustel Y, Jeanrenaud B, Freychet P. Insulin binding and effects in isolated soleus muscle of lean and obese mice. Am J Physiol. 1978 Apr;234(4):E348–E358. [PubMed]
  • Cuendet GS, Loten EG, Jeanrenaud B, Renold AE. Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice. J Clin Invest. 1976 Nov;58(5):1078–1088. [PMC free article] [PubMed]
  • Czech MP, Fain JN. Antagonism of insulin action on glucose metabolism in white fat cells by dexamethasone. Endocrinology. 1972 Aug;91(2):518–522. [PubMed]
  • Czech MP. Regulation of the D-glucose transport system in isolated fat cells. Mol Cell Biochem. 1976 Mar 26;11(1):51–63. [PubMed]
  • Malbon CC, Moreno FJ, Cabelli RJ, Fain JN. Fat cell adenylate cyclase and beta-adrenergic receptors in altered thyroid states. J Biol Chem. 1978 Feb 10;253(3):671–678. [PubMed]
  • Czech MP, Richardson DK, Becker SG, Walters CG, Gitomer W, Heinrich J. Insulin response in skeletal muscle and fat cells of the genetically obese Zucker rat. Metabolism. 1978 Dec;27(12 Suppl 2):1967–1981. [PubMed]
  • Lawrence JC, Jr, Guinovart JJ, Larner J. Activation of rat adipocyte glycogen synthase by insulins. J Biol Chem. 1977 Jan 25;252(2):444–450. [PubMed]
  • Correze C, Auclair R, Nunez J. Cyclic nucleotide phosphodiesterases, insulin and thyroid hormones. Mol Cell Endocrinol. 1976 Jun-Jul;5(1-2):67–79. [PubMed]
  • Correze C, Krug E, Verhaegen M, Nunez J. Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose. Biochim Biophys Acta. 1979 Jul 27;574(1):164–172. [PubMed]
  • Schoenle E, Zapf J, Froesch ER. Receptor binding and effects of insulin and NSILA-S on glucose transport and metabolism in adipocytes from hypophysectomized rats. Diabetologia. 1979 Jan;16(1):41–46. [PubMed]
  • Schoenle E, Zapf J, Froesch ER. Effects of insulin on glucose metabolism and glucose transport in fat cells of hormone-treated hypophysectomized rats: evidence that growth hormone restricts glucose transport. Endocrinology. 1979 Nov;105(5):1237–1242. [PubMed]
  • Schoenle E, Zapf J, Froesch ER. Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats. Am J Physiol. 1979 Oct;237(4):E325–E330. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation