Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP

Galeazza, M.T.; O’Brien, Timothy; Kh, Johnson; Seybold, Virginia S.

doi:10.1016/0196-9781(91)90106-y

Cited by 37 publications

(14 citation statements)

References 25 publications

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“…This finding is supported by previous results in other tissues in 558 which amylin has been shown to compete for CGRP binding sites in the brain, skeletal muscles, and liver of the rat, albeit at a lower affinity than CGRP (35). It has also been shown to mimic the biological effects of CGRP; for example, in guinea pig isolated left atrium and urinary bladder, as well as rat vas deferens, although much higher doses are usually needed to obtain the same effect (36).…”

Section: Discussionsupporting

confidence: 90%

“…This further suggests that the role of amylin in the eye could be related to that of CGRP. Such a conception is supported by the fact that these compounds can bind to each other's receptors, for example, in the rat brain (50), and it seems that there can be different forms of both receptors with differential sensitivity to both peptides (35,51).…”

Section: Discussionmentioning

confidence: 94%

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Amylin Competes for Binding Sites of CGRP in the Chamber Angle and Uvea of Monkey, Cat, and Pig Eye

Alajuuma

Oksala²,

Uusitalo³

2003

Journal of Ocular Pharmacology and Therapeutics

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Calcitonin gene-related peptide (CGRP) binding sites have been identified previously in the eyes of monkey, cat, pig, and guinea pig. In this study, the ability of cat, human, and rat amylins to displace the binding of CGRP in the anterior part of the eye of monkey, cat, and pig was studied. The location and displacement of 125I-hCGRPalpha by amylins as concentrations of 1-1000 nM were studied in cryosections by autoradiography. In the monkey eye, cat and rat amylins were able to compete for the binding sites of CGRP in ciliary muscle and ciliary processes. In the cat eye, cat and human amylins clearly displaced CGRP binding from ciliary muscle, ciliary processes, iris, and chamber angle. Furthermore, rat amylin clearly displaced CGRP binding from ciliary muscle and ciliary processes. In the pig eye, cat, human, and rat amylins competed for the binding sites of CGRP in ciliary muscle, ciliary processes, iris, and limbal conjunctiva. Specific amylin receptors or the possible physiological role of amylin in the eye have not hitherto been reported. It seems, however, that amylin can bind to ocular CGRP receptors and thus probably plays a role in the regulation of the same functions as CGRP, (e.g., aqueous humor outflow).

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Amylin Competes for Binding Sites of CGRP in the Chamber Angle and Uvea of Monkey, Cat, and Pig Eye

Alajuuma

Oksala²,

Uusitalo³

2003

Journal of Ocular Pharmacology and Therapeutics

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“…Similarly, calcitonin-gene-related peptide (CGRP), which shares 46% sequence homology with amylin and modulates K and Ca currents in muscle and nerve (28)(29)(30)(31), reduces insulin secretion from both single rat (8 cells and islets (32,33). Although it is possible that local (3cell effects of amylin are mediated through low-affinity CGRP receptors (34), both amylin secretion from the , cell and its link to type II diabetes make it unique among peptide and hormone modulators of the l3 cell (35,36). Unlike other peptides that are either released from nerve terminals in the endocrine pancreas or from other pancreatic cell types, amylin is cosecreted with insulin from the cell in response to glucose.…”

Section: Resultsmentioning

confidence: 99%

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Wagoner

Chen

Worley

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The release of insulin from the pancreatic ,B cell is dependent upon a complex interplay between stinulators and inhibitors. Recently, amylin, a peptide secreted by pancreatic ,B ceils, has been implicated in the development of type II (noninsulin dependent) diabetes through its modulation of the peripheral effects of insulin. However, the effect of amylin on insulin secretion from the .8 cell has remained controversial.It is reported here that in single ,B cells exhibiting normal glucose sensing, amylin causes membrane hyperpolarization, increases in net outward current, and reductions in insulin secretion. In contrast, in cells with abnormal glucose sensing (e.g., from db/db diabetic mice), amylin has no effect on electrical activity or secretion. Thus, amylin's effects on excitation-secretion coupling in the (8 cell of the pancreas appear to be linked to the cell's capacity for normal glucose sensing.Although the mysteries underlying the effects of glucose and other secretagogues on pancreatic ,B-cell electrical and secretory activity are rapidly unfolding, the mechanisms by which hormones and peptides modulate these activities remain unclear. Certain neuropeptides, released by nerves supplying the pancreas, decrease insulin secretion. This inhibition involves coupling between receptors and ion channels (1). In contrast to such neurotransmitters, it is not known whether and how peptides secreted from the ,B cells themselves affect insulin secretion. Amylin, a 37-aa peptide, is colocalized with insulin in 13-cell secretory granules of human islets (2) and is cosecreted with insulin. It is also the major component of pancreatic islet amyloid commonly found in the pancreases of patients with non-insulin-dependent diabetes mellitus (3). In this disease, loss of normal glucose sensing is one of the earliest defects. Although peripheral actions of amylin have been demonstrated, the influence of amylin on insulin secretion is still debated (4-7). Though the overall role ofamylin in regulating insulin secretion and in the development of diabetes may remain unclear for some time, it is critical to determine the effects of amylin on stimulussecretion coupling at the single-cell level. Thus, we have examined the effects of amylin on excitation and insulin secretion in single isolated pancreatic /3 cells that exhibit normal or abnormal glucose sensing. METHODSTo determine the effects of both glucose and amylin on membrane electrical parameters of single /8 cells, we used the nystatin perforated patch technique (8) to record membrane potentials and ion currents. Detection of insulin secretion from single 13 cells was accomplished using a sequential-cell immunoblot method (9) whereby cells are stimulated to secrete insulin into peptide-retentive immunoblot materialThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. and secreted hormone is quantified by standar...

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“…In vitro experiments using rat hepatocytes have shown either an absence of effects by amylin on insulin-stimulated glucokinase gene expression [22] or a direct effect of amylin to stimulate glycogenolysis and gluconeogenesis [23]. Furthermore, despite the presence of amylin receptors in liver membranes and in a population of hepatic cells [24][25][26], Stephens et al [26] failed to demonstrate a direct effect of amylin on hepatic glucose metabolism. Finally, Nishimura and co-workers reported a lack of effect of amylin on hepatic glucose output in a perfused liver preparation [27].…”

Section: Discussionmentioning

confidence: 99%

S15261 antagonises amylin‐induced impaired glucose tolerance

et al. 1995

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Amylin has been postulated to antagonise or inhibit the action of insulin in peripheral rat tissues and thus contribute to, or be responsible for, the development of insulin resistance. We have recently reported that S15261 is a compound capable of increasing insulin sensitivity in ageing insulin resistant rats. In order to assess whether S15261 had any effects on amylin induced insulin resistance we used a model where amylin causes an impairement in glucose tolerance in an acute manner, by means of an intraportal infusion of the hormone in normal rats. We report here that S15261 can antagonise this amylin-induced impaired glucose tolerance.

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Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP

Cited by 37 publications

References 25 publications

Amylin Competes for Binding Sites of CGRP in the Chamber Angle and Uvea of Monkey, Cat, and Pig Eye

Amylin Competes for Binding Sites of CGRP in the Chamber Angle and Uvea of Monkey, Cat, and Pig Eye

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

S15261 antagonises amylin‐induced impaired glucose tolerance

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