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

Publication ,  Journal Article
Verchere, CB; D'Alessio, DA; Prigeon, RL; Hull, RL; Kahn, SE
Published in: Diabetes
September 2000

Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the pancreatic beta-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 beta-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 microg/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 microg/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 micro 8.7 vs. 80.7 micro 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 approximately 40%, but again had no inhibitory effect on IRI secretion. These data indicate that approximately 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 beta-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.

Duke Scholars

Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

September 2000

Volume

49

Issue

9

Start / End Page

1477 / 1484

Location

United States

Related Subject Headings

  • Rats, Wistar
  • Rats
  • Male
  • Kinetics
  • Islets of Langerhans
  • Islet Amyloid Polypeptide
  • Insulin Secretion
  • Insulin
  • Glucose
  • Endocrinology & Metabolism
 

Citation

APA
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ICMJE
MLA
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Verchere, C. B., D’Alessio, D. A., Prigeon, R. L., Hull, R. L., & Kahn, S. E. (2000). The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells. Diabetes, 49(9), 1477–1484. https://doi.org/10.2337/diabetes.49.9.1477
Verchere, C. B., D. A. D’Alessio, R. L. Prigeon, R. L. Hull, and S. E. Kahn. “The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells.Diabetes 49, no. 9 (September 2000): 1477–84. https://doi.org/10.2337/diabetes.49.9.1477.
Verchere CB, D’Alessio DA, Prigeon RL, Hull RL, Kahn SE. The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells. Diabetes. 2000 Sep;49(9):1477–84.
Verchere, C. B., et al. “The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells.Diabetes, vol. 49, no. 9, Sept. 2000, pp. 1477–84. Pubmed, doi:10.2337/diabetes.49.9.1477.
Verchere CB, D’Alessio DA, Prigeon RL, Hull RL, Kahn SE. The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells. Diabetes. 2000 Sep;49(9):1477–1484.

Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

September 2000

Volume

49

Issue

9

Start / End Page

1477 / 1484

Location

United States

Related Subject Headings

  • Rats, Wistar
  • Rats
  • Male
  • Kinetics
  • Islets of Langerhans
  • Islet Amyloid Polypeptide
  • Insulin Secretion
  • Insulin
  • Glucose
  • Endocrinology & Metabolism