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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent technical advances have yielded considerable new biochemical insights into the hexose transport systems of both brown and white fat cells. In the present studies a novel filtration method was used to monitor initial rates of 3-O-(3H)methylglucose uptake in isolated white fat cells. Transport of 3-O-methylglucose, a non-metabolizable analogue of glucose, occurred by facilitated diffusion, was inhibited by glucose, phloridzin, cytochalasin B and dipyridamole, and was rapidly stimulated by insulin as well as lectins. Total 3-O-methylglucose uptake in white fat cells could be attributed to two kinetically distinct processes in addition to a certain degree of diffusion. Two important new features of glucose transport in fat cells have been discovered. First, in both brown and white fat cells transport per se does not appear to be necessarily rate-limiting for further glucose metabolism. Thus vitamin K5, which markedly increases glucose oxidation by brown fat cells, did not affect the glucose transport system activity. Glucose utilization can apparently be significantly enhanced in fat cells by agents which either increase transport system activity or intracellular enzyme activity. Second, the transport system itself, whether in the basal state or after activation by insulin, lectins, or oxidants, is resistant to sulfhydryl reagents such as N-ethylmaleimide, while the increase in transport activity due to these agents is exquisitely sensitive to sulfhydryl blockage. N-ethylmaleimide blocks the stimulatory effect of insulin on transport whereas addition of insulin to fat cells prior to the reagent completely protects against this inhibitory effect. Further, N-ethylmaleimide prevents the elevated rates of transport system activity due to insulin (or other agents) from returning to basal levels once the cells are washed free of hormone. These data are consistent with the concept that activation of the transport system involves oxidation of key membrane sulfhydryls to the disulfide form, but alternative models are also possible. In any case, these findings provide a possible biochemical clue for future studies designed to identify the specific component(s) involved in the regulatory mechanism which modulates transport of glucose in isolated fat cells.
Mol Cell Biochem 1976 Mar 26
PMID:Regulation of the D-glucose transport system in isolated fat cells. 127 53

1. The disappearance from blood of either 125I-labelled bovine insulin or unlabelled rat insulin after a single intravenous injection has been studied in rats. 2. The disappearance of the labelled insulin was slower than that of native insulin. 3. Ether anaesthesia produced a significant impairment, and bilateral nephrectomy a very marked impairment, of disappearance of the labelled insulin, suggesting that changes in the removal of this tracer may nevertheless parallel changes in the metabolism of native insulin. 4. Simultaneous intravenous injection of unlabelled bovine insulin (1 unit/kg) did not affect disappearance of the labelled insulin. 5. A 20% full-thickness scald injury, produced 2 h previously, had no significant effect on disappearance of the labelled insulin, either with or without the simultaneous administration of unlabelled bovine insulin. 6. The disappearance of unlabelled rat insulin from plasma was also similar in control and scalded rats. 7. It was concluded that the half-life of plasma insulin in the rat, as estimated by either of the techniques used, is not significantly affected by this severe non-haemorrhagic injury.
Clin Sci Mol Med 1976 May
PMID:Disappearance of 125I-labelled and unlabelled insulins from blood in normal and injured rats. 127 46

1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12-40 weeks after the acute episode. 2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover-concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination. 3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover-concentration relaionship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.
Clin Sci Mol Med 1976 May
PMID:Turnover of plasma glucose and free fatty acids in patients on the first day after myocardial infarction. 127 47

1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization. 2. The mean renal extraction of insulin was 0-46, suggesting that the right renal vein should be utilized in comparable studies. 3. No renal extraction of thyroid hormones was detected.
Clin Sci Mol Med 1976 Jun
PMID:The renal handling of insulin and thyroid hormones in normal man. 127 52

The chicken ovalbumin gene is subject to multihormonal regulation. Maximal expression of it requires not only the synergistic effects of estrogen and corticosterone, but also the permissive effects of insulin. In addition to effects on transcription, the stability of its message is greatly enhanced by estrogen. Furthermore, two signal transduction pathways involving protein kinases have been implicated in the regulation of the ovalbumin gene. To better define the role of second messengers on expression of the ovalbumin gene, the effects of the protein kinase-C (PKC) and the cAMP-dependent protein kinase (PKA) pathways on the endogenous levels of ovalbumin mRNA and the transcription of an ovalbumin fusion gene were investigated. Primary cultures of oviduct cells were treated with phorbol 12-myristilate 13-acetate (an activator of PKC) or with forskolin and 3-isobutyl-1-methylxanthine (an activator of PKA) alone, activators plus estrogen and corticosterone, or activators plus both steroids and insulin. The results indicate that phorbol 12-myristilate 13-acetate causes a dramatic destabilization of ovalbumin message, resulting in a reduction in ovalbumin mRNA levels. In contrast, the activators of the PKA system can substitute for insulin and, thereby, increase expression of the ovalbumin gene synergistically with the steroids. The effect of the activators of the PKA system is at the level of transcription. Thus, in chicken oviduct cell cultures, the PKA and PKC signal transduction pathways act in opposing ways to modulate the steroid-induced expression of the ovalbumin gene.
Mol Endocrinol 1992 Sep
PMID:Regulation of expression of the chicken ovalbumin gene: interactions between steroid hormones and second messenger systems. 127 83

Insulin-like growth factors (IGFs) and their binding proteins are implicated in the growth regulation of the kidney during embryogenesis and differentiation. Recent evidence also suggests that IGFs play a role in kidney physiology (glomerular filtration rate, renal plasma flow) and pathology (diabetic renal hypertrophy, nephritis, glomerulosclerosis, kidney tumours, chronic renal failure). This review focuses on the biology of IGFs at the molecular, protein and receptor levels and considers their importance in renal physiology and pathology. The current data demonstrate a central role for the IGFs in the mediation of a wide variety of effects on renal growth, function and malignancy.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney. 127 87

In studies aimed at identifying and characterizing pp60c-src substrates that participate in the enhanced mitogenic response to epidermal growth factor (EGF) observed in murine C3H10T1/2 fibroblasts overexpressing c-src, we have identified a 75-kDa protein (p75) whose properties are consistent with those expected of such a substrate. We present evidence to show that p75 is immunologically related to a recently described, cytoskeleton-associated, pp60v-src substrate [Wu et al. (1991). Mol. Cell. Biol., 11, 5113-5124), and that its phosphotyrosine content is increased cooperatively by c-src overexpression and EGF stimulation. p75 is rapidly (within 2 min) phosphorylated on tyrosine upon EGF treatment and undergoes a second, prolonged phase of tyrosyl phosphorylation from 7 to 21 h after EGF addition, suggesting that tyrosyl phosphorylation of p75 is important for late as well as early events following EGF receptor activation. Enhanced tyrosyl phosphorylation of p75 is also seen when cells overexpressing c-src are treated with platelet-derived growth factor (PDGF), but significantly less phosphorylation is observed with insulin and fibroblast growth factor (FGF). Both basal and EGF-induced tyrosyl phosphorylation of p75 are reduced in cells overexpressing mutated forms of c-src (unmyristylated, or kinase deficient) as compared with wild-type c-src overexpressers, indicating the dependence of the enhanced tyrosyl phosphorylation on membrane-associated, enzymatically active pp60c-src. In cellular fractionation experiments p75 partitions with the cytosol, while immunofluorescence studies reveal a striking colocalization with pp60c-src at the plasma membrane and in the perinuclear region. Partial co-staining of p75 and actin occurs at the cell's periphery. These data provide evidence for p75 being a direct substrate of pp60c-src. The possible role of p75 in the enhanced response to EGF seen in c-src overexpressers is discussed.
 ...
PMID:Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate. 128 4

Insulin-like growth factor-II (IGF-II) mRNA exists as multiple transcript size classes, such as 6.0, 5.3, 4.9, 3.2, and 2.2 kb mRNAs in various human tissues. Three different promoters, 2 different polyadenylation sites, and alternative splicing are involved in producing these multiple transcripts. Initiation of transcription at the 3 different promoters results in multiple mRNAs which contain identical coding regions but different 5'-untranslated regions (5'-UTRs). The first promoter is thought to direct expression of 5.3 kb mRNA in adult human liver. The second promoter region directs expression of 6.0, 3.2, and 2.2 kb mRNAs in human fetal tissues and several adult nonliver tissues. The third promoter specifies transcription of a 4.9 kb mRNA in various tissues. We isolated and sequenced a cDNA clone (pIGF-II-1-70) from a human placental cDNA library, which contains the IGF-II coding region and the 5'-UTR associated with the third promoter. By using a 5'-UTR-specific probe from the clone, we found that this third 5'-UTR is contained in the IGF-II mRNA of 2.2 kb and is absent in the 3.2 kb IGF-II mRNA. We also found an 0.9 kb transcript expressed in placenta, which hybridized strongly to the third 5'-UTR specific probe but not to IGF-II coding region probes. This finding might indicate the existence of an mRNA encoding an IGF-II-associated peptide.
Mol Reprod Dev 1992 Dec
PMID:The third IGF-II promoter specifies transcription of three transcripts out of five in human placenta. 128 23

Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.
Mol Endocrinol 1992 Dec
PMID:Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats. 128 42

Gastric inhibitory polypeptide (GIP), an incretin candidate, is suggested to amplify the glucose-induced insulin secretion. To evaluate its mode of action we examined whether GIP affects 86Rb+ efflux, 45Ca2+ uptake or efflux, and intracellularly recorded electrical activity of mouse pancreatic islets. GIP (5 nM) neither inhibited 86Rb+ efflux at 3 mM glucose nor modulated 86Rb+ efflux that was inhibited by 5.6 mM glucose or stimulated by the calcium ionophore A23187. 45Ca2+ uptake was increased by GIP in the presence of 16.7 mM which was not observed at 3 or 11 mM glucose. GIP elevated 45Ca2+ efflux from islets, but did not modify 45Ca2+ efflux when a virtually Ca2+ free medium was used. Electrical activity of beta cells induced by 16.7 mM glucose was significantly increased by 5 nM GIP. It is concluded that the amplification of insulin release by GIP is based on the effect of GIP on Ca2+ uptake.
Mol Cell Endocrinol 1992 Dec
PMID:Are ionic fluxes of pancreatic beta cells a target for gastric inhibitory polypeptide? 128 94


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