Modulation by Thyroid Status of the Glucagon Receptor-Adenyl Cyclase System in Rat Liver Plasma Membranes*

Hypothyroidism and Glucocorticoids Modulate the Development of Hepatic Insulin Receptors

“…to high ambient insulin concentration, i.e., "down-regulation" Liver plasma membranes were prepared by following the does not occur (13,16). Because, the metabolic effects of insulin method of Neville et al through step 11 (18,28). Briefly, the livers are mediated initially by binding to these specific tissue receptors were hand homogenized by eight strokes in a dounce glass ho- (19), the increased number or affinity of fetal/neonatal insulin mogenizer containing chilled 1 mM bicarbonate buffer.…”

“…Similar effects of hypothyroidism in delaying the normal postnatal maturation of beta adrenergic receptors in lung has recently been reported (3 1). Hypothyroidism also diminishes the number of functional glucagon receptors in adult liver (28) and adrenergic receptors of various adult tissue (29), whereas hyperthyroidism increases the number of insulin receptors of rat adipocytes (1 1).…”

Maternal Diabetes Does Not Alter Postnatal Development of the Hepatic Glucagon Receptor-Adenylate Cyclase System in the Rat

“…Liver plasma membranes. Partially purified (step 11) liver plasma membranes were prepared by the method of Neville et al as previously described from this laboratory (20). In order to perform a complete dose-response curve of glucagon binding and glucagon-stimulated cAMP generation, as well as the cAMP response to sodium fluoride, it was necessary to pool livers from all litters at a given time point to yield a sufficient quantity of membrane.…”

“…Purified crystalline glucagon, a gift of Eli Lilly and Copany, Indianapolis, IN, was used for iodination and displacement. Binding studies were performed in polyethylene tubes as previously described (20). To each tube were added 100 p1 3% BSA in Tris buffer pH 7.6, 50 p1 standard or buffer, 100 p1 buffered hormone (20,000 cpm; approximately 10 pg), and 50 p1 of membrane preparation diluted in Tris buffer to contain 50 pg of protein.…”

“…Binding of ['251]-glucagon to liver plasma membrane was markedly reduced in both IDM and control newborns corresponding to 20,25, and 30% of normal adult values on days 1,7, and 21 of life. Resolution of the curvilinear Scatchard plots of binding data by the two-site model (high affmity-low capacity; low affinity-high capacity) revealed a progressive increase in receptor number (x 10ll/mg protein) of the high affinity sites from 0.9 on day 1 to 1.7 on day 7 and 2.2 on day 21; normal adult was 6.1.…”