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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thr relevance of the crystal structure of the polypeptide hormones, insulin, glucagon and human placental lactogen to conformation and flexibility in solution and to receptor binding is considered. X-ray studies for crystal forms of glucagon, human placental lactogen and three insulin derivatives (A1 acetyl insulin, A1-t-butoxy carbonyl insulin and A1 2,2-dimethyl-3-formyl-L-thiazolidine-4-carbonyl insulin) are reported. Neither glucagon nor human placental lactogen are as ordered as insulin in the crystal form. Glucagon crystals undergo distinct transformations on changing the pH of the mother liquor from pH 9.5 to pH 6, indicating that the glucagon molecule is flexible in the crystal, as it is in solution. On the other hand all insulin analogues have a similar three dimensional structure to that of native insulin. Three dimensional difference Fourier studies of two insulin derivatives at 3 A resolution indicate the position of the modifying groups and define the small conformational changes which have occurred. The in vitro biological activity and receptor binding decrease with the increasing size of the group added to A1. The correlation of the structure analysis with the biological data strongly implicate a region close to A1 in receptor binding. Insulin appears to bind to the receptor in a specific conformation similar to that observed in the crystal structure and in solution; amino acid residues which are separated in the primary structure but brought into close juxtaposition in the tertiary structure are important for full potency.
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PMID:The relation of polypeptide hormone structure and flexibility to receptor binding: the relevance of X-ray studies on insulins, glucagon and human placental lactogen. 17 May 5

The specific binding of 125I-labeled insulin, human hormone ([125I]hGH), bovine growth hormone ([125I]bGH), and ovine prolactin ([125I]oPRL) was studied in mouse liver membranes. [125I]hGH and [125I]oPRL bound to adult liver membranes. Pregnancy increased the specific binding of [125I]hGH but not that of [125I]oPRL. [125I]hGH was displaced from membranes of pregnant mice by hGH, oPRL, and bGH, but only by hGH and oPRL from liver membranes of nonpregnant mice. Significant specific binding of [125I]bGH was seen only in pregnancy. The binding of [125I]bGH to pregnant mouse liver membranes increased with increasing concentration of either membrane protein or [125I]bGH. Both the specific binding and dissociation of [125I]bGH were greatly influenced by the time and temperature of incubation. Binding of [125I]bGH was inhibited by growth hormones, including hGH and rat GH, and not by lactogenic hormones (various prolactins and human placental lactogen), ACTH, glucagon, or insulin. The inhibition of [125I]hGH binding by hGH and bGH, in the presence of excess (2 mug/ml) of PRL, was very similar to that seen with [125I]bGH. Scatchard plots of displacement dose-response curves obtained under steady state conditions of 4C were nonlinear and very similar with either [125I]bGH or [125I]hGH. This contrasted with the linear Scatchard plots obtained from displacement dose-response curves of either [125I]oPRL or [125I]hGH in the presence of excess (2 mug/ml) bGH. Termination of pregnancy, either naturally or by hysterectomy, reduced [125I]bGH specific binding to nonpregnant levels by 24 to 36 h. Estrogen administration did not increase [125I]bGH binding in hepatic membranes. Nonpregnant mice possess hepatic lactogen binding sites which are uninfluenced by pregnancy. GH specific binding sites are markedly augmented during pregnancy. The close correlation between the level of these sites and pregnancy suggests that they are regulated by a product of the fetoplacental unit.
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PMID:Characterization and modulation of growth hormone and prolactin binding in mouse liver. 17 65

Twenty-nine women in premature labor were randomly assigned to a ritodrine (N = 14) or placebo (N = 15) treatment group. Thirteen serial blood samples were drawn during the first 12 hours of therapy by intravenous drug infusion and they were analyzed for a variety of metabolic substances. There was a significant increase in the blood glucose level in the ritodrine group after one hour and this persisted for the 12 hours of intravenous drug treatment. Plasma insulin levels similarly did not increase in the placebo but significantly rose in the ritodrine group by 30 minutes, peaked at 2 1/2 hours, and remained elevated throughout the infusion. There were no significant differences between levels of plasma glucagon, cholesterol triglyceride, human placental lactogen, or human chorionic gonadotropin in the two treatment groups. Ritodrine caused significant maternal and fetal tachycardia. Its use in women with carbohydrate abnormalities should be monitored carefully. The increased glucose levels may lead to an increased fetal weight.
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PMID:The acute effects of ritodrine infusion on maternal metabolism: measurements of levels of glucose, insulin, glucagon, triglycerides, cholesterol, placental lactogen and chorionic gonadotropin. 35 1

To determine the potential of an artificial pancreatic beta cell simulator as a therapeutic and research tool we have used the device for short-term monitoring and control of blood glucose concentrations in five pregnant patients with juvenile-onset diabetes (White's Class C) and three pregnant patients with maturity-onset diabetes (Class B). One patient with brittle juvenile-onset diabetes had successful control before, during, and after cesarean section. The other seven patients were studied during the third trimester of pregnancy and at least four weeks before delivery. Blood glucose control with Biostator regulation was excellent (mean, 96 mg. per deciliter; range, 85 to 107). The insulin requirements needed to achieve optimal glucose control with the Biostator were highly variable (range, 20 to 157 U. per 24 hours) but very similar to those previously calculated to provide optimal control by conventional means. Insulin requirements were unrelated to plasma growth hormone, placental lactogen, or glucagon concentrations. The greatest degree of insulin resistance was seen in obese patients with endogenous insulin-secretory capacity. This study indicates that a pancreatic beta cell simulator can normalize glucose concentrations and rapidly estimate daily insulin requirements in pregnant diabetic patients. In addition, the data suggest that exogenous insulin may indirectly suppress endogenous insulin secretion and thus contribute to the "insulin resistance" of obese patients with maturity-onset diabetes.
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PMID:Studies with a pancreatic beta cell simulator in the third trimester of pregnancies complicated by diabetes. 70 88

The effects of GH, PRL, and placental lactogen (PL) on the proliferation of pancreatic beta-cells in vitro were studied as well as the possible effect of insulin-like growth factor-I (IGF-I) in mediating this effect. Proliferating beta-cells were identified by staining with a monoclonal antibody to bromodeoxyuridine (BrdU) after cells were incubated for 1 h in the presence of 10 microM BrdU. By double staining with insulin antibodies it was found that 6.3% of the beta-cells had incorporated BrdU when cultured for 7 days in the presence of 1 microgram/ml human GH (hGH) compared to 0.6% when cultured in the absence of hGH. Similar results were obtained using rat GH. The half-maximal effect of hGH on beta-cell proliferation was observed at 10 ng/ml, and the maximal effect at 100 ng/ml. Islet cells cultured in the presence of PRL or PL caused a dose-dependent increase in beta-cell proliferation similar to that caused by hGH. GH, PRL, and PL had no effect on the proliferation of glucagon- or somatostatin-producing cells. The addition of 100 ng/ml IGF-I to either control or GH-stimulated islet cells did not affect the labeling index. When GH-stimulated proliferation of beta-cells was measured in the presence of neutralizing concentrations of a rabbit IGF-I antiserum, the percentage of beta-cells incorporating BrdU was unaffected. Using Northern blot analysis, no IGF-I transcripts could be detected in RNA from GH-stimulated islets, whereas IGF-I transcripts were readily detected in RNA isolated from rat liver tissue. These data suggest that the stimulatory effect of GH, PRL, and PL on beta-cell proliferation is not mediated by IGF-I, but, rather, is a direct mitogenic effect on the beta-cell.
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PMID:The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I. 167 31

The lipolytic and antilipolytic effects of human growth hormone (22K-hGH), its 20-kilodalton variant (20K-hGH), a reduced and S-carboxymethylated derivative (RCM-hGH), and human placental lactogen were examined using chicken adipose tissue explants in vitro. Lipolysis, as determined by glycerol release, was stimulated by 22K-hGH (biosynthetic and pituitary derived), 20K-hGH (pituitary derived), and RCM-hGH (modified biosynthetic). These growth hormone preparations also exhibited similar antilipolytic activity (i.e., transient inhibition of glucagon-induced lipolysis). However, unlike human growth hormone, human placental lactogen neither stimulated lipolysis nor inhibited glucagon-stimulated lipolysis. Some augmentation of glucagon-stimulated lipolysis was observed in the presence of human placental lactogen. These results indicate that the disulfide bridges (Cys53----Cys165; Cys182----Cys189) and amino acid residues 32-46 of hGH are not required for lipolytic or antilipolytic activities of human growth hormone on chicken adipose tissue.
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PMID:Lipolytic and antilipolytic effects of human growth hormone, its 20-kilodalton variant, a reduced and carboxymethylated derivative, and human placental lactogen on chicken adipose tissue in vitro. 232 May 98

Glucagon's effect on the placenta was studied in cultured human term trophoblast and in homogenized term and first-trimester placentas. In studies with cultured term trophoblast, glucagon stimulated the generation of cyclic AMP and estradiol secretion and inhibited placental lactogen secretion. Incubation of homogenates of term and of first-trimester placenta with 0.5 mM dibutyryl cAMP revealed a marked decrease of pyruvate kinase activity. Glucagon produced a similar decrease in first-trimester homogenates, but failed to affect term placentas. The present demonstration of the placenta as a target tissue for glucagon suggests an active contribution of the trophoblast to energy metabolism during pregnancy.
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PMID:The human placenta as a target tissue for glucagon. 283 52

The effect of ovine placental lactogen (oPL) on glucagon-stimulated glycogenolysis was studied in cultured hepatocytes from 20-day-old fetal rats. Pretreatment of hepatocytes with oPL (0.5-5 micrograms/ml) significantly attenuated the inhibitory effect of glucagon on glycogen synthesis. Hepatocytes exposed to glucagon alone at 1, 5, and 20 nM incorporated 32.0, 43.2, and 62.1% less [14C]glucose into glycogen than control hepatocytes. However, hepatocytes pretreated for 1 h with oPL (1 microgram/ml) and then exposed to the same concentration of glucagon incorporated only 5.8, 9.2, and 22.1% less [14C]glucose than control cells (P less than 0.01 vs. glucagon alone). In cells preincubated for 24 h in medium containing [14C]glucose, glucagon reduced cellular [14C]glycogen and total glycogen content by 47.1 and 51.0% while oPL increased total cellular glycogen content by 105.8% and attenuated the glycogen-degradative effect of glucagon. While oPL alone had no effect on basal phosphorylase a (Pa) activity, oPL (1-10 micrograms/ml) caused a 15.3-91.6% inhibition of glucagon-stimulated Pa activity (P less than 0.01). The maximal inhibition by oPL of glucagon-stimulated Pa activity occurred within 2 min of exposure to oPL, and the effect was not blocked by cycloheximide. oPL also caused a 49.4-95.0% inhibition of (Bu)2cAMP-stimulated Pa activity (P less than 0.01), suggesting that the inhibitory effect of oPL on glucagon action is exerted, at least in part, at a site distal to the intracellular accumulation of cAMP. Insulin (1 microM) reduced basal Pa activity, abolished the stimulation of Pa activity by glucagon, and markedly attenuated the stimulation of Pa by (Bu)2-cAMP. These studies demonstrate that oPL acutely inhibits glycogen degradation in fetal rat hepatocytes and suggest that oPL promotes glycogen storage in fetal liver both by antagonizing the glycogenolytic effects of glucagon and by stimulating fetal hepatic glycogenesis.
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PMID:Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes. 298 83

To determine which hormones might regulate somatomedin secretion in the fetus, we measured somatomedin levels in conditioned medium from primary cultures of fetal rat hepatocytes. We employed a bioassay [( 3H]thymidine incorporation into DNA of chick embryo fibroblasts), a displacement assay [competition for binding of radiolabeled multiplication-stimulating activity (rat insulin-like growth factor II) to the somatomedin-binding protein] for total somatomedin, and the RIA for somatomedin-C. Epidermal growth factor and dexamethasone were the most active hormones tested; total somatomedin levels were 2-3 times above control levels. Rat GH was much less stimulatory. Human placental lactogen, glucagon, and insulin had little or no effect. Stimulation of somatomedin secretion by both epidermal growth factor and dexamethasone was time and dose dependent. The maximal response occurred at 48 h at a concentration of about 1 X 10(-7) M of either hormone. In the bioassay, stimulation by epidermal growth factor, but not dexamethasone, was detected. The steroid enhanced the secretion of an inhibitor that completely masked the mitogenic activity of the increased somatomedin levels. The somatomedin secreted by fetal hepatocytes exhibited immunological cross-reactivity with human somatomedin-C, but the levels were 500-fold less than those measured by our displacement assay. This suggests that the predominant fetal rat somatomedin is not somatomedin-C. We conclude that epidermal growth factor and dexamethasone, but not GH or placental lactogen, stimulated the secretion by fetal hepatocytes of a somatomedin which resembled multiplication-stimulating activity.
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PMID:Hormonal regulation of somatomedin secretion by fetal rat hepatocytes in primary culture. 387 Oct 85

Pregnancy is characterized by a rapid accumulation of lipid stores during the first half of gestation and a utilization of these stores during the latter half of gestation. Lipogenesis results from dietary intake, an exaggerated insulin response, and an intensified inhibition of glucagon release. Increasing levels of placental lactogen and a heightened response of adipose tissue to additional lipolytic hormones balance lipogenesis in the fed state. Maternal starvation in late gestation lowers insulin, and lipolysis supervenes. The continued glucose drain by the conceptus aids in converting the maternal liver to a ketogenic organ, and ketone bodies produced from incoming fatty acids are not only utilized by the mother but cross the placenta where they are utilized in several ways by the fetus: as a fuel in lieu of glucose; as an inhibitor of glucose and lactate oxidation with sparing of glucose for biosynthetic disposition; and for inhibition of branched-chain ketoacid oxidation, thereby maximizing formation of their parent amino acids. Ketone bodies are widely incorporated into several classes of lipids including structural lipids as well as lipids for energy stores in fetal tissues, and may inhibit protein catabolism. Finally, it has recently been shown that ketone bodies inhibit the de novo biosynthesis of pyrimidines in fetal rat brain slices. Thus during maternal starvation ketone bodies may maximize chances for survival both in utero and during neonatal life by restraining cell replication and sustaining protein and lipid stores in fetal tissues.
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PMID:Ketone body metabolism in the mother and fetus. 388 90


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