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(Received for publication, August 30, 1994; and in revised form, October 14, 1994) 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
Volume 270,
Number 3,
Issue of January 20, 1995 pp. 1295-1299
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
-Cells in Obesity
EVIDENCE FOR INDUCTION OF FUNCTIONAL, MORPHOLOGIC, AND METABOLIC
ABNORMALITIES BY INCREASED LONG CHAIN FATTY ACIDS
10 times that of controls, whereas
-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 K glucose metabolism and
-cell hyperplasia, abnormalities that can be induced in normal
islets by increased FFA.
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R. Aalinkeel, M. Srinivasan, S. C. Kalhan, S. G. Laychock, a |
