Biomedical subjects

P L Surface

Publications and source records attributed to P L Surface.

5 recordsLinked to original sources

PubMed1998

Changes in leptin expression are not associated with corresponding changes in CCAAT/enhancer binding protein-alpha.

C/EBP-alpha binds a C/EBP consensus site in the leptin promoter and activates transcription in vitro. We assessed adipose tissue expression of C/EBP-alpha, leptin and beta-actin in Sprague Dawley rats under conditions that modulate leptin mRNA abundance in order to study the relationship between leptin and C/EBP-alpha expression patterns. During acute fasting, which decreased the level of leptin and beta-actin mRNA, C/EBP-alpha mRNA expression was unaltered. In leptin-treated and pair-fed animals, C/EBP-alpha mRNA was unaltered compared to ad libitum fed controls, while leptin and beta-actin mRNA expression was again decreased. These results indicate that changes in the level of leptin gene expression are not directly associated with changes in the level of C/EBP-alpha abundance.

Adipose Tissue↗

PubMed1998

Differentiation method-dependent expression of leptin in adipocyte cell lines.

Leptin, the product of the ob gene, is expressed exclusively in adipose tissue. However, adipocyte cell lines, such as 3T3-L1 adipocytes, have generally been reported to express extremely low levels of leptin mRNA. We compared 3T3-L1's to the closely related line 3T3-F442A, and to another murine adipocyte line, TA1. TA1 cells, when differentiated by indomethacin/insulin treatment, express leptin at levels greater than those of 3T3-L1 adipocytes differentiated by the traditional methylisobutylxanthine/dexamethasone/insulin protocol. However, when 3T3-L1's are differentiated in the presence of indomethacin/insulin their expression levels of leptin increase dramatically. 3T3-F442A preadipocytes also express high levels of leptin when differentiated in the presence of T3 and insulin, but when differentiated in the presence of indomethacin/insulin, expression levels drop precipitously. These changes in leptin mRNA and protein expression are not reflected by changes in CCAAT/enhancer binding protein-alpha (c/EBPalpha), peroxizomal proliferator activated receptor-gamma (PPARgamma), lipoprotein lipase (LPL), fatty-acid binding protein aP2 or uncoupling protein-2 (UCP2) mRNA levels, and suggest a mechanism unique to the leptin gene.

3T3 Cells↗

PubMed1997

Modifications in the B10 and B26-30 regions of the B chain of human insulin alter affinity for the human IGF-I receptor more than for the insulin receptor.

Inversion of the natural sequence of the B chain of human insulin (HI) from ProB28LysB29 to LysB28ProB29 generates an insulin analogue with reduced tendency to self-associate. Since this substitution increases the homology of insulin to insulin-like growth factor-I (IGF-I), we have examined the affinity of a series of insulin analogues with the general modified structure XaaB28ProB29 HI for binding to both human placental insulin and IGF-I receptors. The XaaB28ProB29 HI series is approximately equipotent to HI in binding to the insulin receptor with the exception of when Xaa = Phe, Trp, Leu, Ile, and Gly (40-60% relative to HI). Substitution with basic residues in the B28 position increased the relative affinity to the IGF-I receptor approximately 1.5-2-fold (ArgB28ProB29 > OrnB28ProB29 = LysB28ProB29). Substitution with acidic residues reduced relative affinity for the IGF-I receptor approximately 2-fold (CyaB28ProB29 = GluB28ProB29 > AspB28ProB29). Combination of AspB10 substitution in conjunction with a modification in the B28-29 position (e.g. AspB10LysB28ProB29 HI) showed an additional 2-fold selective increase in affinity for the IGF-I receptor, suggesting that these two effects are additive. Addition of Arg residues at B31-32, on the backbone of either HI or AspB10 HI, increased affinity for the IGF-I receptor 10 and 28 fold, respectively, compared to HI, confirming the significance of enhanced positive charge at the C-terminal end of the insulin B-chain in increasing selectivity for the IGF-I receptor. This relative increase in IGF-I receptor affinity correlated largely, but not completely, with enhanced growth promoting activity in human mammary epithelial cells. In the case of LysB28ProB29 HI, growth activity correlated with dissociation kinetics from the insulin receptor which were shown to be identical with those of human insulin.

Amino Acid Sequence↗

PubMed1996

Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP.

Regulation of obese gene (ob) expression in ob/ob and db/db mice and in cultured rat adipocytes was examined. It has been demonstrated that exogenous human OB protein (leptin) treatment reduces food intake and weight gain, as well as insulin, glucose, and corticosterone levels in ob/ob mice. In the present report we show that leptin treatment down-regulates endogenous adipose ob mRNA. However, treatment of isolated rat adipocytes with 100 ng/ml human or murine leptin had no direct effect on expression of endogenous ob mRNA, suggesting that leptin may be able to down-regulate its own expression by an indirect, non-autocrine mechanism. Glucocorticoids increased both ob mRNA levels and secreted leptin levels in vitro. Conversely, agents that increase intracellular cAMP, such as beta-adrenergic agonists or Bt2cAMP itself, decreased ob mRNA expression and leptin secretion. Therefore, increased glucocorticoid levels and decreased sympathetic neural activity may contribute to the elevated ob mRNA expression observed in genetically obese, hyperglucocorticoid rodents. Furthermore, leptin might regulate its own expression through a feedback mechanism involving the hypothalamic pituitary axis.

Adipocytes↗

PubMed1990

Sexual dimorphic porcine pituitary response to growth hormone-releasing hormone.

The aim of this study was to compare growth hormone (GH) response of barrows and gilts to porcine growth hormone-releasing hormone (pGRH) at the pituitary level. Anterior pituitary cells from barrows and gilts responded to pGRH in a dose-dependent manner. The median effective pGRH concentration (EC50) which stimulated GH release from cells of barrows was greater (P less than .05) than that for cells obtained from intact female siblings. Maximal pGRH mediated GH secretion from barrows was not different (P greater than 0.05) than that from gilt stimulated cells. These data demonstrate that somatotrophs of growing peripubertal gilts are more responsive to pGRH stimulation than are cells from their castrated male siblings. This difference could be caused by castration of the neonatal male.

Animals↗