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

Abstract

The studies described in this paper were undertaken to characterize the circulating and hepatic insulin and glucagon receptor concentrations of control (C), diabetic (Db), and pinealectomized-diabetic (Pn + Db) rats. Compared with C rats, an increase in plasma glucose and glucagon levels and a reduction in circulating insulin concentrations in Db animals was observed; these differences were greater in Pn + Db rats. In liver membranes, insulin binding was lower in Db and in Pn + Db than in C rats, and glucagon binding was greater in Db and in Pn + Db than in C rats. The modifications in hormone binding did not reflect changes 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 and their receptors was similar in all three groups. These findings indicate that in either pinealectomized-diabetic or diabetic rats there were significant changes in the circulating and liver insulin and glucagon receptor concentrations and that the changes in the circulating levels of both pancreatic hormones were more pronounced in pinealectomized-diabetic animals. In addition, the absence in Db and in Pn + Db rats of the insulin and glucagon down-regulation of their own receptors could further modify metabolic activities in these animals.

Identification of a novel human glucagon receptor promoter: Regulation by cAMP and PGC-1α

“…Prolonged fasting however upregulated glucagon receptor mRNA in the liver (Burcelin et al, 1998), with refeeding normalizing the glucagon receptor mRNA levels. We and others have also observed a stimulatory effect of high glucose on glucagon receptor mRNA expression in both cultured rat islets and hepatocytes (Krones et al, 1998) and this has been confirmed in vivo where the level of glucagon receptor mRNA was increased in diabetic animals (Burcelin et al, 1998;Mellado et al, 1989). Finally, we and others have shown that glucocorticoids inhibit glucagon receptor mRNA expression in both cultured rat islets and adipocytes Calle et al, 1987).…”

Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8)

“…n08 animals per group (van Cauter et al 1991;Peschke and Peschke 1998). Pinealectomy induced diminished glucose tolerance, insulin resistance, decreased hepatic and muscular glycogenesis and an increase in blood pyruvate concentration in rats (Mellado et al 1986). On the other hand, it has been shown that melatonin was able to reduce insulin secretion under several experimental conditions (Peschke and Peschke 1998;la Fleur et al 1999;la Fleur 2001).…”

Receptor (MT1) mediated influence of melatonin on cAMP concentration and insulin secretion of rat insulinoma cells INS‐1

“…Inconsistent data appeared in the last decades on the influence of the pineal gland on the secretion of insulin, on blood glucose as well as on the carbohydrate metabolism. For instance it has been postulated that melatonin or some other pineal compounds exerts an insulin‐like effect accompanied by hypoglycemia and increased glucose tolerance, which was supported by the observation that pinealectomy diminished glucose tolerance, decreased hepatic and muscular glycogenesis and increased blood pyruvate level [1–5]. In agreement it was observed that pinealectomy or sympathetic denervation of the pineal gland causes hyperglycemia together with paradiabetic metabolic disturbances [6, 7] which were reduced or prevented by application of melatonin.…”