Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids

Joseph L. Milburn, Hiroshi Hirose, Young H. Lee, Yoshitaka Nagasawa, Atsushi Ogawa, Makoto Ohneda, Hector BeltrandelRio, Christopher B. Newgard, John H. Johnson, Roger H. Unger

Research output: Contribution to journalArticle

264 Citations (Scopus)

Abstract

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 ∼10 times that of controls, whereas β-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 β-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

Original languageEnglish
Pages (from-to)1295-1299
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number3
Publication statusPublished - 1995 Jan 20
Externally publishedYes

Fingerprint

Fatty Acids
Nonesterified Fatty Acids
Glucose
Insulin
Rats
Obesity
Zucker Rats
Hyperinsulinism
Bromodeoxyuridine
Cell Size
Metabolism
Hyperplasia
Wistar Rats
Pancreas
Volume fraction
Oxidation
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Milburn, J. L., Hirose, H., Lee, Y. H., Nagasawa, Y., Ogawa, A., Ohneda, M., ... Unger, R. H. (1995). Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. Journal of Biological Chemistry, 270(3), 1295-1299.

Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. / Milburn, Joseph L.; Hirose, Hiroshi; Lee, Young H.; Nagasawa, Yoshitaka; Ogawa, Atsushi; Ohneda, Makoto; BeltrandelRio, Hector; Newgard, Christopher B.; Johnson, John H.; Unger, Roger H.

In: Journal of Biological Chemistry, Vol. 270, No. 3, 20.01.1995, p. 1295-1299.

Research output: Contribution to journalArticle

Milburn, JL, Hirose, H, Lee, YH, Nagasawa, Y, Ogawa, A, Ohneda, M, BeltrandelRio, H, Newgard, CB, Johnson, JH & Unger, RH 1995, 'Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids', Journal of Biological Chemistry, vol. 270, no. 3, pp. 1295-1299.
Milburn, Joseph L. ; Hirose, Hiroshi ; Lee, Young H. ; Nagasawa, Yoshitaka ; Ogawa, Atsushi ; Ohneda, Makoto ; BeltrandelRio, Hector ; Newgard, Christopher B. ; Johnson, John H. ; Unger, Roger H. / Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 3. pp. 1295-1299.
@article{ea3cd9a9d4314b0c962c495b650c0de1,
title = "Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids",
abstract = "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 ∼10 times that of controls, whereas β-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 β-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.",
author = "Milburn, {Joseph L.} and Hiroshi Hirose and Lee, {Young H.} and Yoshitaka Nagasawa and Atsushi Ogawa and Makoto Ohneda and Hector BeltrandelRio and Newgard, {Christopher B.} and Johnson, {John H.} and Unger, {Roger H.}",
year = "1995",
month = "1",
day = "20",
language = "English",
volume = "270",
pages = "1295--1299",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids

AU - Milburn, Joseph L.

AU - Hirose, Hiroshi

AU - Lee, Young H.

AU - Nagasawa, Yoshitaka

AU - Ogawa, Atsushi

AU - Ohneda, Makoto

AU - BeltrandelRio, Hector

AU - Newgard, Christopher B.

AU - Johnson, John H.

AU - Unger, Roger H.

PY - 1995/1/20

Y1 - 1995/1/20

N2 - 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 ∼10 times that of controls, whereas β-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 β-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

AB - 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 ∼10 times that of controls, whereas β-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 β-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

UR - http://www.scopus.com/inward/record.url?scp=0028985060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028985060&partnerID=8YFLogxK

M3 - Article

C2 - 7836394

AN - SCOPUS:0028985060

VL - 270

SP - 1295

EP - 1299

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -