Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.
 ...
PMID:Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat. 256 32

1. The IGF-I concentrations in colostrum on days 1 and 2 after parturition were higher than those in cow and neonate plasma. 2. The modest increase in GH concentrations in cow plasma around parturition would not be enough to stimulate IGF-I release by tissues. 3. The concentrations of insulin, GH and glucagon in colostrum were substantially lower than those in plasma.
 ...
PMID:Insulin-like growth factor-I, GH, insulin and glucagon concentrations in bovine colostrum and in plasma of dairy cows and neonatal calves around parturition. 257 66

Starvation, glucagon and cyclic AMP inhibit, and refeeding starved animals and insulin or IGF-I plus triiodothyronine stimulate accumulation of FAS and its mRNA in liver; transcription is the primary regulated step. In the uropygial gland, differentiation of basal cells into mature sebocytes is accompanied by the accumulation of large amounts of FAS and its mRNA. By analogy with liver, transcription is likely to be the regulated step, but direct experimental evidence for this hypothesis is lacking. FAS mRNA is a unique gene and is probably more than 100 kb in length. The FAS gene of goose and duck is transcribed into two mature mRNAs of about 10,800 and 12,200 nucleotides. The 3'-untranslated regions of the FAS mRNAs contain an unusual polypyrimidine tract which, at the mRNA level at least, appears unrelated to regulation of gene expression. Polypyrimidine tracts similar in sequence to that in the FAS gene are found in about 20 different parts of the genome. All of the fragments which contain these tracts are hypermethylated. The next stage of this investigation will involve identification of cis-acting sequence elements in the FAS gene which specify responses to diet, hormones and tissue-specific regulatory factors. Isolation and characterization of the 5'-ends of the cDNA and the gene are underway.
 ...
PMID:Structure and regulation of the avian gene for fatty acid synthase. 259 Mar 94

We have evaluated the pharmacokinetics, reliability and patient tolerability of a newly developed injection pen for cartridged growth hormone (GH). The cartridge contains 25 IU GH in 2 ml solvents. The pen, which is basically a needle, syringe and vial in one piece, is operated by a turning movement and allows doses from 0.25-4 IU. Nine GH deficient patients were hospitalized twice for overnight bloodsampling following subcutaneous injections (at 8 p.m.) of GH: i.e. when using traditional syringe and vial and after 6 weeks of use of the pen. Serum GH antibodies were measured immediately prior to, and 3 and 6 months following pen treatment. GH containers were collected regularly from the patients for chemical analysis. A questionnaire was completed during and at the end of the study. The absorption rate and bioavailability of GH tended to be higher with syringe and vial (2 P = 0.07) but there were no differences in the profiles of IGF-I, insulin, glucagon or pertinent metabolic parameters following the 2 injection modes. No GH antibodies occurred during 6 months of pen treatment. The content of polymeric GH was lower in the cartridges (2 P less than 0.001). Seven of the patients reported less injection pain when using the injection pen, which they all strongly preferred and wished to continue using. We conclude that the GH injection pen is a reliable tool which seems to be more convenient for the patients.
 ...
PMID:Growth hormone administration by means of an injection pen. 281 89

Purified rat pancreatic islet cells express somatomedin receptors which are identified by their affinity for insulin-like growth factor (IGF)-I, IGF-II, and insulin. Binding of [125I]IGF-I to islet A cells was half-maximally inhibited by 7.10(-10) M IGF-I, while IGF-II, insulin, and proinsulin were respectively 10-, 500-, and 10,000-fold less potent displacers of IGF-I binding. Unrelated hormones such as glucagon or GH did not compete with [125I]IGF-I binding to A cells. The concentration of IGF-I receptors on A cells was estimated at 5000 IGF-I binding sites per cell with affinity constant (Ka) of 2 X 10(9) M-1. Islet B cells were found to exhibit a reversible time- and temperature-dependent binding with [125I]IGF-I. Specificity and affinity of IGF-I binding sites were identical for islet A and B cells. Linear Scatchard plots of competitive binding data on B cells suggest 1 single class of IGF-I receptors in a concentration of 12,000 sites per cell. The presence of high affinity receptors for IGF-I on adult islet A and B cells provides a molecular basis for this growth factor to influence growth, survival, and/or function of these endocrine cell types. Their low affinity for insulin should be considered as a potential mechanism for this hormone to influence, at high concentration, the function of islet A and B cells.
 ...
PMID:Evidence for the presence of type I insulin-like growth factor receptors on rat pancreatic A and B cells. 295 69

The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal islet-like cell clusters during long-term tissue culture. 305 61

In the submitted review the author discusses two substances secreted into the circulation which can similarly as insulin lower the blood sugar level. These substances are IGF-I (insulin-like growth factor I) and GLP (glucagon-like peptide). While in case of the former it is not certain whether it participates in the glucose homeostasis, this is beyond doubt in the latter. IGF-I prepared by the recombinant technique can be used therapeutically in cases of insulin resistance caused by a receptor or postreceptor disorder, because it may act via its own receptor. Side-effects after larger doses are a problem. GLP-1, the use of which would be useful in type 2 diabetics as it stimulates insulin secretion, is not used so far in therapy because hitherto prepared preparations have a very short period of a effectiveness.
 ...
PMID:[Factors with insulin-like effects: IGF-I and GLP-1]. 748 55

In previous studies it was shown that bovine GH (bGH) and glucagon, when individually added to primary rat hepatocyte cultures, modestly stimulated IGF-I mRNA levels 1.8- to 2.5-fold, but when combined, synergized to stimulate IGF-I mRNA levels by 10- to 12-fold. In the present study we have explored further the mechanism of this effect in primary rat hepatocyte cultures. Like glucagon, the addition of 3-isobutyl-1-methylxanthine (100 microM) or (Bu)2cAMP (150 microM) augmented IGF-I mRNA levels 1.8- to 2.0-fold, but when combined with bGH (50 ng/ml), they augmented levels up to 12-fold. The half-life of IGF-I mRNA, determined by incubating hepatocytes with actinomycin-D was 12 h. Although bGH did not affect the decay rate, glucagon (100 ng/ml) or (Bu)2cAMP (100 microM) reduced the rate of loss by about 70%. 4 beta-Phorbol 12 beta-myristate 13 alpha-acetate minimally stimulated IGF-I mRNA levels 1.2- to 1.4-fold, but displayed no synergism when added with bGH, glucagon, or (Bu)2cAMP. The stimulatory effect of bGH plus glucagon was inhibited 80% after preincubation with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (10 microM) for 24 h. The addition of staurosporine, sphingosine, or H-7 [1-(5-isoquinolinyl sulfonyl)2-methyl piperazine] inhibited the stimulatory effect of bGH plus glucagon on hepatocyte IGF-I mRNA by 80%, 90%, and 85%, respectively. Preincubation with cycloheximide (10 micrograms/ml) blocked the synergistic effect of bGH plus either glucagon or (Bu)2cAMP by 65-80%. The effect of glucagon, mediated via the activation of adenylate cyclase, involves in part the posttranscriptional stabilization of IGF-I mRNA levels. The effect of GH, mediated in part by the activation of protein kinase-C, appears to be at the level of transcription. The synergistic augmentation of hepatocyte IGF-I mRNA levels by GH and glucagon involves the activation of PKA and PKC, but also appears to require the synthesis of one or more protein(s).
 ...
PMID:The augmentation of insulin-like growth factor-I messenger ribonucleic acid in cultured rat hepatocytes: activation of protein kinase-A and -C is necessary, but not sufficient. 750 34

[125I]IGF-I binding to chicken hepatoma cell (LMH) membranes was displaced by unlabelled IGF-I or IGF-II, but not by insulin. Cross-linking revealed specific binding sites of 128 and 28-31 kDa, which following solubilization could be separated by wheat germ agglutinin (WGA) chromatography. [125I]IGF-I binding to the WGA eluate (128 kDa) could be displaced by insulin although with a 30-fold lower potency than IGF-I. Binding to the WGA flow-through (28-31 kDa) was not inhibited by insulin. This suggested that IGF binding to LMH was due mainly to membrane bound IGFBP rather than to type 1 IGF receptors. A reverse proportion was observed in normal chicken liver. A predominant 28 kDa IGFBP was synthesized and secreted by LMH cells, together with an unusual 60 kDa IGF binding entity which only bound [125I]IGF-II (with weak affinity). This process was not affected by the presence or absence of glucose, dexamethasone, glucagon, insulin or IGF-I.
 ...
PMID:Preferential binding of insulin-like growth factors to a binding protein rather than to receptors on chicken hepatoma cell (LMH) membranes. 753 43

Regulation of the production of insulin-like growth factor (IGF)-I, IGF-II, IGF binding proteins (IGFBPs), and their related proteins by various hormones was investigated in primary cultures of rat liver parenchymal and nonparenchymal cells. Freshly isolated parenchymal cells contained mRNAs of IGF-I, IGF-II, IGFBP-1, IGFBP-4, growth hormone (GH) receptor, and the acid-labile subunit (ALS), which forms a ternary complex with IGF-I and IGFBP-3; however, parenchymal cells did not express the IGFBP-3 gene. In contrast, nonparenchymal cells contained IGFBP-3 mRNA exclusively, as we reported previously [Takenaka et al. Agric. Biol. Chem., 55, 1191-1193 (1991)]. Cultured rat parenchymal cells produced IGF-I, IGFBP-1, and IGFBP-4 prominently. In these cells, secretion of IGF-I and the content of IGF-I mRNA was greatly increased in the presence of GH in the medium. Insulin also increased the production of IGF-I. Secretion of IGFBP-1 into the medium was enhanced by treatment with glucagon, dibutyrylcyclic AMP (Bu2cAMP), and dexamethasone (Dex) and these enhancements with glucagon and Dex reflected the increase in its mRNA content. Insulin depressed the secretion of IGFBP-1. The content of IGFBP-4 in the parenchymal cells was increased by insulin, Bu2cAMP, and triiodothyronine (T3), thereby enhancing the production of IGFBP-4 and secretion into the medium. Cultured liver nonparenchymal cells of rats produced IGFBP-1, IGFBP-3, and IGFBP-4. Secretion of IGFBP-1 was increased by Bu2cAMP in the medium, that of IGFBP-3 by IGF-I, and that of IGFBP-4 by both IGF-I and Bu2cAMP. Regulation of the production of IGFBP-3 by IGF-I was demonstrated in these investigations. These results suggest that GH increases production of IGF-I in the parenchymal cells and this IGF-I, in turn, increases the production of IGFBP-3 in nonparenchymal cells. As we found GH also increases ALS production in parenchymal cells, by these mechanisms, GH increases the formation of the ternary complex of IGF-I, IGFBP-3, and ALS. This study clearly demonstrates the interrelationship between parenchymal and nonparenchymal cells in the production of IGF-I and IGFBPs in the liver.
 ...
PMID:Production of insulin-like growth factors and their binding proteins in primary cultures of rat liver parenchymal and nonparenchymal cells. 754 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>