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M Freemark

Publications and source records attributed to M Freemark.

46 records · Page 3Linked to original sources
PubMed1985

Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes.

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.

Animals↗
PubMed1985

Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes.

The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen (14.4-72.9%; P less than 0.001) and total cell glycogen content (10.6-34.3%; P less than 0.01). Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [14C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism.

Animals↗
PubMed1984

Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes.

Vasopressin, angiotensin and phenylephrine stimulate glycogenolysis in postnatal rat liver by a Ca2+-mediated mechanism not involving cyclic AMP. To determine whether these hormones promote glycogenolysis in foetal liver, we have examined their effects, and those of the Ca2+ ionophore A23187, on glycogen metabolism in cultured foetal-rat hepatocytes. Vasopressin and angiotensin (0.1 nM-0.1 microM) had no effects on either glycogen synthesis (as assessed by [14C]glucose incorporation into glycogen) or phosphorylase a activity. However, A23187 at 1 and 10 microM inhibited glycogen synthesis by 31.3 and 89.1% respectively (both P less than 0.001) and stimulated phosphorylase a activity by 66.9 and 184.1% respectively (both P less than 0.01). Incubation of cells in Ca2+-deficient medium attenuated the effects of 10 microM-A23187 on glycogen synthesis and abolished the effects of 1 microM-A23187. As in postnatal liver, glucagon (1 and 20 nM) and isoprenaline (1 and 10 microM), which activate adenylate cyclase, inhibited glycogen synthesis and stimulated phosphorylase a activity in foetal hepatocytes. The minimal effective concentration of phenylephrine was 10 times that of isoprenaline. These results indicate striking differences in the ontogeny of cyclic AMP-mediated and Ca2+-mediated processes which regulate hepatic glycogenolysis. Since increases in cytosolic Ca2+ induce glycogenolysis in foetal-rat liver, the weak or absent responses to vasopressin, angiotensin and the alpha-adrenergic agonists may result from defects in hormone-receptor binding or in post-receptor events leading to the mobilization of intracellular Ca2+ stores.

Angiotensin II↗
PubMed1984

Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes.

The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen and total cellular glycogen content after 4 h of incubation but had no effect on glycogen degradation. Half-maximal stimulation occurred with an oPL concentration of 3 micrograms/ml. In contrast, human placental lactogen had no effect on [14C]glucose incorporation into glycogen. Ovine growth hormone (50 and 100 micrograms/ml), rat growth hormone (20, 40, and 100 micrograms/ml), and ovine prolactin (10, 40, and 100 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen, but the potencies of these hormones were only 10-20% of that of oPL. Insulin (20 nM) stimulated [14C]glucose incorporation into glycogen, whereas glucagon (0.5 and 20 nM) inhibited [14C]glucose incorporation into glycogen and increased glycogen degradation. Our findings suggest that oPL may have direct insulin-like effects on carbohydrate metabolism in the fetus and that oPL may contribute to the accumulation of fetal liver glycogen that occurs in late gestation.

Animals↗
PubMed1984

Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes.

The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75-22.5 micrograms/ml) and insulin (0.01-1 microM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen. However, the dose-response curves for the two hormones were not parallel and the maximum effect of oPL was 3.4 times greater than that of insulin (P less than 0.001). The two hormones had synergistic effects on [14C]glucose incorporation at low concentrations and additive effects at maximum concentrations. Ovine growth hormone (oGH) also stimulated [14C]glucose incorporation into glycogen but with a potency only 12.3% that of oPL. Cycloheximide (20 microM) abolished the stimulation of [14C]glucose incorporation by insulin (1 microM), oPL (5 micrograms/ml), and oGH (100 micrograms/ml). Although the glycogenic actions of oPL and insulin may depend on new protein synthesis, the results of these studies suggest that these hormones stimulate glycogen synthesis in fetal liver by different mechanisms. Because the glycogenic actions of oPL are potentiated by insulin, these hormones may act in concert to promote hepatic glycogen storage in the fetus.

Animals↗
PubMed1983

Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm.

Previous studies from this laboratory indicate that ovine placental lactogen (oPL) and ovine growth hormone (oGH) stimulate amino acid transport in diaphragms of postnatal rats with equal potencies. However, in studies reported here using diaphragms from fetal rats on day 20 of gestation, oPL (2,5 and 20 micrograms/ml) stimulated a dose-dependent increase in amino acid uptake, while oGH (5,20 and 100 micrograms/ml) and rat growth hormone (rGH, 2 and 40 micrograms/ml) were without effect. The effect of oPL on fetal AIB transport was neither enhanced nor antagonized by oGH (100 microgram/ml). The magnitude of stimulation of AIB transport by oPL was comparable to that observed with insulin (100 and 1000 microU/ml). Human placental lactogen (hPL) and ovine prolactin (oPRL) had no effect on fetal AIB transport. Since oPL is present in high concentrations in fetal blood, these studies suggest that oPL may have a direct role in the regulation of fetal amino acid and protein metabolism, that oPL and oGH may bind to different receptors in fetal rat tissues, and that oPL may function as a "fetal growth hormone".

Amino Acids↗
PubMed1981

Case report. Atypical findings in adrenoleukodystrophy.

Computed tomography (CT) in a child with typical clinical and biochemical features of adrenoleukodystrophy (ALD) revealed striking pathologic enhancement in the centra semiovalia, posterior corpus callosum, and corticospinal tracts within the internal capsules, cerebral peduncles, and basis pontis. Central calcifications were detected within otherwise typical symmetrical low attenuation lesions in the periatrial white matter. These findings further expand the spectrum of CT abnormalities in ALD and may represent a link between the recently described Type 1 and Type 11 CT patterns.

Adrenal Glands↗
PubMed1979

Streptobacillary rat-bite fever: a pediatric problem.

A case of streptobacillary rat-bite fever in an 11-year-old boy from rural North Carolina is described. The child's clinical course was unique in that he developed a subglottic mass and bilateral parotid swelling. He responded initially to tetracycline but relapsed after therapy. Cure was ultimately achieved with a three-week course of penicillin. A review of the literature concerning this unusual clinical entity is presented.

Child↗
PubMed1978

Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats.

Testosterone pretreatment (1.0-4.0 mg/kg) attenuated, in a dose-response fashion, the induction of stereotyped behavior and hyperactivity by pargyline (0.25, 4.0 mg/kg) and beta-phenylethylamine (8.0, 16.0 mg/kg) in preubertal, male rats. The dyskinetic movements induced by pargyline and beta-phenylethylamine were proposed as a possible animal model for tardive dyskinesias. Attenuation by testosterone of these effects suggested an hormonal involvement consistent with the reported predominant occurrence of tardive dyskinesias in women and in the elderly.

Animals↗