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

Abstract

SummaryWe examined the postnatal maturation of the glucagon receptor-adenylate cyclase system of liver plasma membrane from rats born to normal or streptozotocin-induced diabetic mothers and compared results to those of nonpregnant adult. Diabetes in mothers was confirmed by hyperglycemia (458 zk 41 versus 128 f 13 mg/dl; mean + S.E.) and relative hypoinsulinemia (4.3 + 1.0 versus 7.4 f 1.0 ng/ml) when compared to controls. Pups born to diabetic mothers (IDM) were hyperglycemic (59 f 6 versus 23 + 5 mg/dl) but not significantly hyperinsulinemic (4.3 + 0.5 versus 3.5 k 0.6 ng/ml) when compared to control pups on day 1; by day 7 and on day 21 glucose and insulin were similar in IDM and control pups. 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

Pre‐ and Postnatal Development of Insulin and Glucagon Receptors

“…The developmental pattern of glucagon receptors is in striking contrast to that of the insulin receptor as outlined in Table 1 (11,12,14). There is general agreement that glucagon receptors of fetal liver have decreased or at best equal affinity to the corresponding glucagon receptor of adult liver.…”

“…Insulin receptors of the developing mannnalian fetus and in the newbo rn period have been studied on circulating cells such as erythrocytes and monocytes as well as in isolated hepatocytes or liver plasma membranes (2,(9)(10)(11)(12).…”

“…~1en the Scatchard plots are curvilinear, there are at least two orders of binding qites termed high affinity-low capacity, or low affinity-high capacity which can also be resolved from the Scatchard plots by appropriate calculations with the X-intercepts reflecting receptor number and the slopes receptor affinity. Alternatively, curvilinear Scatchard plots may be considered as a single order of binding sites with negative cooperativity (2,(9)(10)(11)(12).…”

“…Although glucagon receptors are present in fetal liver, their decreased number limits the amount of cyclic NIP that may be formed in response to glucagon. In addition, there is evidence in some species that glucagon receptors of fetal liver, even when present, are functionally unlinked, or incompletely linked to the adenylate cyclase system so that even at maximal doses, glucagon elicits only a small cyclic M~response (11,12,14). This defect is restricted to the glucagon receptor, the adenylate cyclase complex itself being functional and intact since other stimuli such as prostaglandin El, sodium fluoride and cholera toxin can elicit appropriate cyclic Mr esponses (11,14).…”

Effect of Dexamethasone on the Adenylate Cyclase System of Cultured Hepatocytes of Fetal Rats

“…There have been several reports concerning the ontogeny of glucagon receptors in tissues such as liver and heart [2,3], The number of glucagon receptors is known to be lower in the fetus and newborn and to increase grad ually to reach adult levels during the first few weeks of life [4]. In spite of several reports regarding the ontogénie pattern of peptide hormone receptors, there is some inconsis tency in various studies on the maturation of the post-receptor complex axis, which in volves the guanosine-5'-triphosphate (GTP) regulatory and catalytic components [5,6].…”