Secretion of islet amyloid polypeptide in response to glucose

Kanatsuka, Azuma; Makino, Hideichi; Ohsawa, Haruhiko; Tokuyama, Yoshiharu; Yamaguchi, Tetsuro; Yoshida, Sho; Adachi, Masakazu

doi:10.1016/0014-5793(89)81527-3

Cited by 109 publications

(52 citation statements)

References 15 publications

(4 reference statements)

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“…In advanced type II diabetes, local amylin excesses (24) could further contribute to the inability of the ,B cell to accurately sense and respond to normal variations in glucose levels. Although it is impossible to precisely measure the local concentration of amylin as it is secreted from the 3 cell, local concentrations up to 10-8 M have been estimated (25,26). Effects seen in this study were robust at this concentration, as well as at lower and higher concentrations (0.1-500 nM).…”

Section: Resultsmentioning

confidence: 60%

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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Section: Resultsmentioning

confidence: 60%

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 isolated-perfused pancreas, primary islets, or b-cell models have shown that amylin secretion can be stimulated by many factors, including glucose, arginine, and fatty acids, and that amylin secretion tracks insulin secretion (Kanatsuka et al, 1989;Ogawa et al, 1990;Qi et al, 2010). Pancreatic b cells are the major source of circulating plasma amylin, which ranges from 3-5 pM in the fasting state to postprandial concentrations of 15-25 pM (Lutz, 2006;.…”

Section: B Amylin Expression Secretion and Metabolismmentioning

confidence: 99%

Amylin: Pharmacology, Physiology, and Clinical Potential

Hay¹,

Chen²,

Lutz³

et al. 2015

Pharmacol Rev

291

297

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“…IAPP is synthesized primarily in the pancreatic ␤-cell, where it is colocalized with insulin in secretory granules (4,5) and is released along with insulin in response to stimulation by ␤-cell secretagogues such as glucose (6,7). The physiological function of IAPP has not been determined, although effects on insulin action (8) and secretion (9), gastric emptying (10), and food intake (11) have all been suggested.…”

mentioning

confidence: 99%

The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells.

et al. 2000

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Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the pancreatic ␤-cell that is cosecreted with insulin and is the major constituent of islet amyloid deposits in individuals with type 2 diabetes or insulinomas. We have previously reported that glucose stimulates IAPP, but not insulin secretion, from neonatal rat ␤-cells when regulated secretion is prevented by use of calcium-free media, suggesting that IAPP secretion occurs via a constitutive secretory pathway. To directly test this hypothesis, we examined the effects of 2 substances-brefeldin A (BFA) and cycloheximide (CHX)-that are predicted to selectively block constitutive secretion on the release of IAPP-like immunoreactivity (IAPP-LI) and immunoreactive insulin (IRI) from neonatal rat islet cell monolayer cultures. When regulated release was prevented by use of calcium-free media, glucose-stimulated IAPP-LI release was nearly abolished by blocking constitutive release with 10 µg/ml BFA (mean ± SD: 8.7 ± 7.7 vs. 29.3 ± 14.3 pmol/l; n = 5; P < 0.05), an inhibitor of constitutive vesicle formation. Similarly, calcium-independent, glucose-stimulated IAPP-LI secretion was markedly suppressed when new protein synthesis was blocked by administration of 20 µg/ml CHX (4.6 ± 2.1 vs. 29.5 ± 14.0 pmol/l; n = 5; P < 0.005). Secretion of IRI was low in the absence of calcium, and neither BFA nor CHX had any further effect. When calcium was added to the incubation media to allow regulated secretion of both IRI and IAPP-LI, both BFA (47.7 ± 8.7 vs. 80.7 ± 10.3 pmol/l; P < 0.001) and CHX (37.3 ± 5.8 vs. 73.3 ± 6.2 pmol/l; n = 5; P < 0.0001) inhibited glucose-stimulated IAPP-LI secretion by ~40%, but again had no inhibitory effect on IRI secretion. These data indicate that ~40% of glucose-stimulated IAPP-LI release occurs via a constitutive secretory pathway in neonatal rat islet cells. By contrast, in adult rat islets, glucose-stimulated IAPP-LI release was almost abolished in the absence of calcium (86 ± 3% inhibition; P < 0.05) and unaffected by addition of BFA (275 ± 28 vs. 205 ± 89 pmol/l; NS) or CHX (160 ± 20 vs. 205 ± 89 pmol/l; NS), suggesting that constitutive secretion of IAPP does not occur in mature ␤-cells. Collectively, these data suggest that a significant proportion of glucose-stimulated IAPP secretion from neonatal, but not adult, rat islet cells occurs via a constitutive secretory pathway.

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Secretion of islet amyloid polypeptide in response to glucose

Cited by 109 publications

References 15 publications

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

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

Amylin: Pharmacology, Physiology, and Clinical Potential

The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells.

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