Metabolic effects of 3-iodothyronamine in hepatocytes
S. Ghelardoni, G. Chiellini, S. Frascarelli & R. Zucchi
3-iodothyronamine (T1AM) is an endogenous thyroid hormone derivative which produces profound metabolic effects such as a shift in fuel substrate utilization from carbohydrates to lipid. Thus, in the present work we investigated the effects of T1AM on hepatic glucose metabolism.
To assess metabolite release, human hepatocellular carcinoma cells (HepG2) were exposed for 4 h to different concentrations of exogenous T1AM (0.1, 1 and 10 μM) in glucose production buffer (DME base containing pyruvate and lactate). Cell culture medium was then collected and glucose and ketone body (acetoacetate and β-hydroxybutyrate) levels were evaluated. In addition, isolated rat liver preparations were perfused either with Krebs-Henseleit buffer or glucose production buffer containing 1 μM T1AM. The effluent perfusate was then collected for 60 min at 5 min intervals to measure the release of glucose and ketone bodies (acetoacetate and β-hydroxybutyrate).
In HepG2, only infusion with 1 μM T1AM induced a significant increase in glucose production (9.11±0.37 vs 7.48±0.14 μg/mg of total proteins in cell lysate, P<0.01), and a significant decrease in acetoacetate release (252.4±10.5 vs 286.8±7.2 nmol/ mg of total proteins in cell lysate P<0.05).
Liver perfusion with glucose production buffer in the presence of 1 μM T1AM also showed a significant increase of glucose production (0.555±0.062 vs 0.369±0.043 mg/min per g P<0.05), while infusion with Krebs-Henseleit buffer did not produce any significant change in glucose metabolism.
In conclusions our preliminary data suggested that T1AM stimulated gluconeogenesis and inhibited ketogenesis under conditions of glucose deprivation.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.