Effect of Pinealectomy on Liver Insulin and Glucagon Receptor Concentrations in the Rat

Abstract

The studies described here were undertaken to characterize the hepatic insulin and glucagon receptors of control (C), pinealectomized (Pn), and melatonin-treated pinealectomized (Pn + Mel) rats. Compared with C rats, an increase in plasma glucose and glucagon levels and a reduction in circulating concentrations of insulin in Pn animals were observed. Melatonin treatment of Pn rats reverses all three parameters toward the normal values. In liver membranes, insulin binding was lower in Pn than in C rats, and glucagon binding was greater in Pn than in C animals; in Pn + Mel rats both insulin and glucagon binding reverse toward the normal values that were observed in C rats. The modifications in hormone binding reflect changes in the number of receptors but not in the affinity constants. The time courses of hormone association and dissociation from liver membranes were similar in all three experimental groups. The degradation of both hormones by liver membranes was similar in all three groups. Insulin receptor degradation also was similar in the three groups, while glucagon receptor degradation was similar in the liver membranes of C and Pn rats but smaller in Pn + Mel animals. These findings suggest that the pineal gland may modulate the circulating levels and liver receptor concentrations of insulin and glucagon. In addition, our results indicate that insulin and glucagon did not induce a down-regulation of liver receptors in Pn rats.

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

“…On the other hand, the high melatonin plasma levels in streptozotocin rats were associated with increased expression of Aanat mRNA [21]. These results are in agreement with observations that administration of melatonin [22][23][24][25][26][27] or pinealectomy [28,29] affect metabolic disturbances related to plasma insulin and diabetes [19]. Using the LEW.1AR1-iddm rat, we analysed the situation in a spontaneous animal model of human type 1 diabetes.…”

Effects of Pinealectomy on Glucagon Responsiveness to Hypoglycaemia Induced by Insulin Injections in Fed Rats

“…Experiments were carried out during the light period (ZT 4), for comparison with published results, because in previous studies on the effects of pinealectomy on glucose metabolism in which the time of day was stated, experiments were carried out during the daytime (Diaz & Blazquez, 1986;Lima et al 1998). Rats were given free access to food and water because previous results indicated that the pineal gland and melatonin do not affect the maintenance of normal circadian periodicities in food and water intake, or body weight gain (Zanoboni et al 1978;Rodriguez et al 1989). This was confirmed by our results, which showed no difference in body weight between the rats of the three groups, and no change in glycaemia and hormonal levels measured at the same time during the nycthemeron in the three groups.…”

The influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar:Han rats

“…It was demonstrated that MEL enhances the insulin level in plasma of pinealectomized rats (Diaz & Blazquez, 1986), reduces insulin secretion from pancreatic islets cells in vitro (Peschke et al, 1997) or has no effect on pancreatic insulin release (Frankel & Strandberg, 1991). MEL alters concentrations of insulin and glucagon receptors in the liver (Rodriguez et al, 1989) and enhances the catecholamines content in the adrenal medulla (Mahata et al, 1988). Moreover, the existence of central site of MEL effects in the brain is assumed in the suprachiasmatic nucleus of hypothalamus (Shima et al, 1997).…”

“…Concerning the carbohydrate metabolism, hyper-and hypoglycemic effects of MEL were found in experimental animals after pinealectomy and after the exogenous MEL treatment. It was documented that pinealectomy induced hyperglycemia (Rodriguez et al, 1989) or hypoglycemia (Gorray et al, 1979) and exogenous MEL administration increases (Dhar et al, 1983), decreases (Mahata et al, 1988) or have no influence on the blood glucose level (John et al, 1990). Mechanism, which is involved in modulation of the plasma glucose by MEL, remains unknown.…”