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  • 1
    Electronic Resource
    Electronic Resource
    Cellular basis of direct insulin action in the central nervous system (1981)
    Springer
    Diabetologia 20 (1981), S. 255-267 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; insulin receptors ; circumventricular organs ; hormone feedback
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo radioautographic method has been applied to elucidate the mechanism of direct peptide hormone “feedback” action in the CNS. Using this method we have identified the circumventricular organs of the brain as general endocrine target tissues for a variety of blood-borne polypeptide hormones, including insulin. In the arcuatemedian eminence region of the hypothalamus blood-borne insulin directly interacts with receptive nerve terminals, suggesting that insulin acts to influence the electrical activity of select hypothalamic nerve circuits at the level of synaptic transmission. Recent results obtained from preliminary surgical and chemical lesion studies of brain indicate that insulin-receptive nerve terminals in the arcuate-median eminence region arise from neurons intrinsic to the medial basal hypothalamus. This has lead us to propose the concept of the hypothalamic tuberoinfundibular insulin-receptive neuron and its axon collaterals as a pathway for the centripetal flow of insulin “signals” in the form of electrical impulses. We envisige that the neuroanatomic pathway, provided by the hypothalamic tuberoinfundibular neuron, functions to link changes in body metabolic activity, as reflected in changing levels of circulating insulin, to the neuronal process of elaborating specific central metabolic-regulatory programs. This pathway could be of key importance in understanding and combating metabolic disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254491
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  • 2
    Electronic Resource
    Electronic Resource
    Peroxovanadate and insulin action in adipocytes from NIDDM patients. Evidence against a primary defect in tyrosine phosphorylation (1997)
    Springer
    Diabetologia 40 (1997), S. 1197-1203 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Peroxovanadate ; insulin ; isoprenaline ; cAMP ; lipolysis ; glucose uptake ; tyrosine phosphorylation ; NIDDM ; adipocyte ; in vitro.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effects of insulin and the stable peroxovanadate compound potassium bisperoxopicolinatooxovanadate (bpV(pic)), a potent inhibitor of phosphotyrosine phosphatases, on lipolysis and glucose uptake in subcutaneous adipocytes from 10 male patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 matched non-diabetic control subjects. Lipolysis stimulated by isoprenaline or the cAMP analogue, 8-bromo-cyclic AMP (8-br-cAMP), was reduced by approximately 40 % in NIDDM compared to control subjects. In both groups bpV(pic) exerted an antilipolytic effect that was similar to insulin (∼ 50 % inhibition). 14C-U-glucose uptake was dose-dependently increased by bpV(pic) treatment, but this effect and also that of insulin were impaired in NIDDM compared to control (bpV(pic) 1.6-fold vs 2.4-fold and insulin 2.2-fold vs 3.4-fold). Furthermore, low concentrations of bpV(pic) did not affect insulin-stimulated glucose uptake, although tyrosine phosphorylation of the insulin receptor β-subunit was clearly increased by bpV(pic). In conclusion, 1) β-adrenergic stimulation of lipolysis in vitro is attenuated in NIDDM adipocytes due to post-receptor mechanisms. 2) Both insulin and bpV(pic) decrease lipolysis and enhance glucose uptake in control as well as NIDDM adipocytes. The effect on glucose uptake, but not that on lipolysis, is impaired in NIDDM cells. 3) Peroxovanadate does not improve sensitivity and responsiveness to insulin in NIDDM adipocytes, showing that insulin-resistant glucose uptake in NIDDM is not overcome by phosphotyrosine-phosphatase inhibition and, thus, probably is not caused by impaired tyrosine phosphorylation events alone. [Diabetologia (1997) 40: 1197–1203]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050807
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  • 3
    Electronic Resource
    Electronic Resource
    A stable peroxovanadium compound with insulin-like action in human fat cells (1996)
    Springer
    Diabetologia 39 (1996), S. 235-242 
    Details
    ISSN: 1432-0428
    Keywords: Adipocytes ; insulin ; vanadate ; peroxovanadate ; glucose uptake ; lipolysis ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aqueous solutions of peroxovanadium (pV) compounds are potent insulin-mimics in various types of cell. Since chemical instability is a problem with these agents, we studied the insulin-like action in human fat cells of a stable pV complex, bpV(pic). It enhanced 14C-U-glucose uptake in a dose-dependent manner by approximately twofold which was slightly less than the effect of insulin (approximately threefold). The pV complex did not alter cell-surface insulin binding and submaximal concentrations did not influence cellular sensitivity to insulin action on glucose uptake. The bpV(pic) inhibited the lipolytic effect of isoprenaline to the same extent as insulin; however, when the cGMP-inhibitable low-Km phosphodiesterase (cGI-PDE) was blocked with the specific inhibitor OPC 3911, the antilipolytic effect of insulin, but not that of bpV(pic), was completely prevented. Moreover, when lipolysis was stimulated by the non-hydrolysable cAMP analogue N6-monobutyryl cAMP, bpV(pic), in contrast to insulin, maintained an antilipolytic effect. These findings indicate that bpV(pic) exerts its antilipolytic effect not only through cGI-PDE activation, similar to the effect of insulin, but also by means of other mechanisms. The tyrosine kinase activity of insulin receptors from human placenta was not altered by the pV compound itself, whereas bpV(pic) clearly enhanced insulin-stimulated activity. In contrast, in situ tyrosine phosphorylation of the insulin receptor Β-subunit as well as that of several other proteins was clearly increased in cells which were treated with bpV(pic), whereas vanadate only amplified insulin-stimulated tyrosine phosphorylation. In conclusion, bpV(pic) exerts powerful insulin-like effects in human fat cells and may be a new and potentially useful agent in the management of insulin-resistant states.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403968
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  • 4
    Electronic Resource
    Electronic Resource
    Peroxovanadate but not vanadate exerts insulin-like effects in human adipocytes (1993)
    Springer
    Diabetologia 36 (1993), S. 113-116 
    Details
    ISSN: 1432-0428
    Keywords: Vanadate ; peroxovanadate ; adipose cells ; lipolysis ; glucose transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vanadate and peroxovanadate were recently reported to exert maximal or even supramaximal (peroxovanadate) insulin-like effects in rat adipocytes. To evaluate the response in human cells, isolated human adipocytes were exposed to insulin or various concentrations of vanadate (0–10 mmol/l) or peroxovanadate (0–5 mmol/l). Neither vanadate nor peroxovanadate affected 125I-insulin binding and insulin sensitivity. Vanadate exerted no apparent effect on 14C-U-glucose uptake, whereas 0.1 mmol/l peroxovanadate exerted a full insulin-like response (p〈0.001). No additive response was observed by combining either vanadate or peroxovanadate with insulin. Peroxovanadate at 0.1 mmol/l was as effective as insulin in inhibiting isoproterenol-stimulated lipolysis. Neither peroxovanadate nor insulin-inhibited lipolysis stimulated by N6-monobutyryl-cAMP, an analogue which is not hydrolysed by the cAMP-phosphodiesterase. It is concluded that peroxovanadate, but not vanadate, elicits a full insulin-like response in human adipocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400690
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  • 5
    Electronic Resource
    Electronic Resource
    Characterization of lactogen binding sites in choroid plexus (1983)
    Springer
    Experimental brain research 49 (1983), S. 300-306 
    Details
    ISSN: 1432-1106
    Keywords: Choroid plexus ; Lactogen ; Radioautography ; Receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prolactin binding sites have been demonstrated previously in rat choroid plexus using in vivo radioautography (Walsh et al. 1978). In the present study we have employed this procedure to characterize further the binding specificity of these sites. Following the injection of 125 I-hGH or 125I-oPRL an intense radioautographic reaction was observed over the choroid plexus. The reaction was significantly reduced by coinjecting excess unlabeled hGH or oPRL but not bGH. The specific binding of 125I-oPRL to choroid plexus from rat, rabbit, sheep and pig was demonstrated by in vitro assays. Subsequently a survey of 125I-oPRL specific binding in a number of regions of pig brain indicated that the highest binding was in choroid plexus. A detailed study of the characteristics of 125I-oPRL binding to pig choroid plexus was undertaken. Specific binding increased with choroid plexus homogenate protein to a maximum of 30% (3.0 mg protein/tube). Binding was maximum at 4 ° C by 30–40 h of incubation. During the incubation the integrity of 125I-oPRL in the incubation medium declined steadily to 50% after 20 h and 35–40% after 48 h. Radioactivity eluted from binding sites was fully intact as judged by rebinding to lactogen receptor-enriched membranes. Binding showed a broad pH optimum of 5.5–7.5. On cell fractionation of choroid plexus binding sites were enriched in microsomes. The binding of 125I-oPRL and 125I-hGH was inhibited in a dose-dependent manner by unlabeled lactogens and was of high affinity. hGH and oPRL were equipotent inhibitors of the binding of both radioligands whereas bGH and a variety of structurally unrelated peptides were noninhibitory. These studies indicate rat choroid plexus binds lactogens other than prolactin as do other wellcharacterized lactogen receptors. Furthermore, the in vitro binding studies on pig brain have demonstrated notable enrichment of lactogen binding sites in choroid plexus and have indicated that they have characteristics of lactogen receptors. The physiologic significance of our findings is unknown but the presence of lactogen receptors in choroid plexus raises the possibility of its being a target organ for prolactin. It is also possible that the receptors play a role in transporting prolactin from the blood to the CSF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238589
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  • 6
    Electronic Resource
    Electronic Resource
    Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone: Evidence for a prolactin “short-loop” feedback site (1980)
    Springer
    Experimental brain research 38 (1980), S. 455-461 
    Details
    ISSN: 1432-1106
    Keywords: “Short-loop” feedback ; Prolactin ; Reproduction ; Median eminence ; Receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence. Following systemic injection 125I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of 125I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine growth hormone, competitively blocked 125I-human growth hormone binding to the external median eminence. These observations provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effects of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237526
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  • 7
    Electronic Resource
    Electronic Resource
    Catalytic antibodies: Perusing combinatorial libraries
    Amsterdam : Elsevier
    Trends in Biochemical Sciences 19 (1994), S. 145-150 
    Details
    ISSN: 0968-0004
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0968-0004(94)90273-9
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  • 8
    Electronic Resource
    Electronic Resource
    A revised strategy for cloning antibody gene fragments in bacteria
    Amsterdam : Elsevier
    Gene 128 (1993), S. 111-117 
    Details
    ISSN: 0378-1119
    Keywords: Artificial operon ; affinity-tail sequence ; coliphage T3 promoter ; combinatorial library ; monocistronic expression ; plaque-lift assay
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0378-1119(93)90161-U
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  • 9
    Electronic Resource
    Electronic Resource
    Uptake of Insulin and Other Ligands into Receptor-Rich Endocytic Components of Target Cells: The Endosomal Apparatus (1985)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 47 (1985), S. 383-403 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.47.030185.002123
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  • 10
    Electronic Resource
    Electronic Resource
    Receptors for insulin-like growth factors in rabbit articular and growth plate chondrocytes in culture
    Amsterdam : Elsevier
    Experimental Cell Research 148 (1983), S. 105-116 
    Details
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0014-4827(83)90191-X
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