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Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.

Publication ,  Journal Article
Milburn, JL; Hirose, H; Lee, YH; Nagasawa, Y; Ogawa, A; Ohneda, M; BeltrandelRio, H; Newgard, CB; Johnson, JH; Unger, RH
Published in: J Biol Chem
January 20, 1995

To elucidate the mechanism of the basal hyperinsulinemia of obesity, we perfused pancreata from obese Zucker and lean Wistar rats with substimulatory concentrations of glucose. Insulin secretion at 4.2 and 5.6 mM glucose was approximately 10 times that of controls, whereas beta-cell volume fraction was increased only 4-fold and DNA per islet 3.5-fold. We therefore compared glucose usage at 1.4, 2.8, and 5.6 mM. Usage was 8-11.4 times greater in Zucker islets at 1.4 and 2.8 mM and 4 times greater at 5.6 mM; glucose oxidation at 2.8 and 5.6 mM glucose was > 12 times lean controls. To determine if the high free fatty acid (FFA) levels of obesity induce these abnormalities, normal Wistar islets were cultured with 0, 1, or 2 mM long chain FFA for 7 days. Compared to islets cultured without FFA insulin secretion by FFA-cultured islets (2 mM) perifused with 1.4, 3, or 5.6 mM glucose was increased more than 2-fold, bromodeoxyuridine incorporation was increased 3-fold, and glucose usage at 2.8 and 5.6 mM glucose was increased approximately 2-fold (1 mM FFA) and 3-fold (2 mM FFA). We conclude that hypersecretion of insulin by islets of obese Zucker fatty rats is associated with, and probably caused by, enhanced low Km glucose metabolism and beta-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 20, 1995

Volume

270

Issue

3

Start / End Page

1295 / 1299

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats, Wistar
  • Rats
  • Obesity
  • Male
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Hexokinase
  • Glucose
 

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Milburn, J. L., Hirose, H., Lee, Y. H., Nagasawa, Y., Ogawa, A., Ohneda, M., … Unger, R. H. (1995). Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. J Biol Chem, 270(3), 1295–1299. https://doi.org/10.1074/jbc.270.3.1295
Milburn, J. L., H. Hirose, Y. H. Lee, Y. Nagasawa, A. Ogawa, M. Ohneda, H. BeltrandelRio, C. B. Newgard, J. H. Johnson, and R. H. Unger. “Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.J Biol Chem 270, no. 3 (January 20, 1995): 1295–99. https://doi.org/10.1074/jbc.270.3.1295.
Milburn JL, Hirose H, Lee YH, Nagasawa Y, Ogawa A, Ohneda M, et al. Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. J Biol Chem. 1995 Jan 20;270(3):1295–9.
Milburn, J. L., et al. “Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.J Biol Chem, vol. 270, no. 3, Jan. 1995, pp. 1295–99. Pubmed, doi:10.1074/jbc.270.3.1295.
Milburn JL, Hirose H, Lee YH, Nagasawa Y, Ogawa A, Ohneda M, BeltrandelRio H, Newgard CB, Johnson JH, Unger RH. Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. J Biol Chem. 1995 Jan 20;270(3):1295–1299.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 20, 1995

Volume

270

Issue

3

Start / End Page

1295 / 1299

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats, Wistar
  • Rats
  • Obesity
  • Male
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Hexokinase
  • Glucose