Triiodo-L-thyronine stimulates glycogen synthesis in rat hepatocyte cultures

Abstract

The hyperthyroid state is associated with low hepatic glycogen levels, but paradoxically with a high activity of glycogen synthase and low activity of glycogen phosphorylase. We determined the effects of triiodo-L-thyronine (T3) on glycogen synthesis and glycogen synthase activity in rat hepatocytes in vitro. Culture of rat hepatocytes with T3 (100 nM-1 microM) for 16 h-40 h increases glycogen synthesis from glucose and gluconeogenic precursors. The stimulation of glycogen synthesis by T3 was associated with an increase in the activity of glycogen synthase and was additive with the long-term effects of insulin but not with the short-term stimulation of glycogen synthesis by insulin. Culture of hepatocytes with T3 (at concentrations up to 1 microM) did not affect the responsiveness of glycogen synthesis to short-term stimulation by insulin but culture with 10 microM-T3 decreased the responsiveness to insulin without affecting the basal rate. It is suggested that the high activity of glycogen synthase in the hyperthyroid state is due to a direct effect of T3 on the hepatocyte, but the low hepatic glycogen content is probably due to either secondary metabolite and/or endocrine changes or to impaired responsiveness to insulin. T3 may have an anabolic role in the control of hepatic glycogen storage in the euthyroid postprandial state.

Direct effects of iodothyronines on excess fat storage in rat hepatocytes

“…Experiments with THs require a physiological concentration of 1% BSA (4 Â 10 À5 M) that sequesters a large amount of iodothyronines because of its high affinity constant (k a for T 3 about 2 Â 10 5 mol À1 ) [45]. Moreover, the concentrations of T 2 and T 3 (10 À6 to 10 À5 M) that were effective in our study on primary hepatocytes from euthyroid rats are within the range reported to stimulate lipogenesis [15] and glycogen synthesis [46] in hepatocytes from hypothyroid rats.…”

In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone

“…An induction of the ␤ 2 -adrenergic receptor mRNA was observed consistent with the positive effects of T3 observed in human adipose tissue (Viguerie et al 2002) and rat liver (Feng et al 2000). As shown in hepatocytes (Swierczynski et al 1991;Betley et al 1993), T3 up-regulated enzymes involved in gluconeogenesis and glycogen metabolism (Table 5). Numerous genes of mitochondrial energy metabolism were up-regulated, including several enzymes associated with the citric acid cycle.…”

The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism

“…The analysis of various kinds of literature data and the results obtained in our work allow us to suggest that the response of animals to excess of thyroid hormones is multiphase. Betley et al (1993) and Müller and Seitz (1980) stated stimulatory effect of thyroid hormones on gluconeogenesis. Simultaneously, we found out the dramatic reduction of glycogen content in the liver.…”