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Cited by 374

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

A 48-hour Lipid Infusion in the Rat Time-Dependently Inhibits Glucose-Induced Insulin Secretion and B Cell Oxidation Through a Process Likely Coupled to Fatty Acid Oxidation*

SAKO, YASUHIRO, GRILL, VALDEMAR E.·1990·Endocrinology
DOI 10.1210/endo-127-4-1580
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Abstract

Short- and long-term effects of hyperlipidemia with elevated FFA on insulin secretion were investigated. Male Sprague-Dawley rats were fed ad libitum and additionally infused with Intralipid 10%, 1.0 ml/h. After 3 h of Intralipid the response to 27 mM glucose in isolated perfused pancreas was enhanced by 86%, P less than 0.02. After 6 h of Intralipid enhancement had subsided. After 48 h of Intralipid glucose-induced insulin release was inhibited by 49%, from 1950 +/- 177 microU/min after saline to 1003 +/- 232 microU/min after Intralipid, P less than 0.02. Inhibition was glucose-selective since responses to other secretagogues (1 mM 3-isobutyl-1 methylxanthine, 10 mM octanoate, or 5 mM alpha-ketoisocaproic acid) were unaffected as were pancreatic contents of insulin (2284 +/- 111 mU/pancreas after saline, 2566 +/- 131 mU/pancreas after Intralipid). In isolated islets from 48 h lipid infused rats production of [14-C]CO2 from D[U-14-C]glucose was decreased (P less than 0.02) in parallel with the insulin response to 27 mM glucose. Glucose-induced secretion was partially normalized by in vitro exposure to a carnitine palmitoyl-transferase I inhibitor (Etomoxir). Effects of a 48 h lipid infusion were also tested during hyperglycemia. Rats were infused with glucose, and hyperglycemia was enhanced by dexamethasone (25 micrograms/24 h). Hyperglycemia depressed glucose-induced secretion from perfused pancreas from 2072 +/- 22 microU/min after saline + dexamethasone to 1185 +/- 155 microU/min after glucose + dexamethasone, P less than 0.01). Intralipid, added to the latter protocol, further inhibited glucose-induced secretion to 437 +/- 87 microU/min, P less than 0.005. Hyperlipidemia is concluded to be associated with short term stimulation but long term inhibition of glucose-induced insulin secretion. Evidence indicates that inhibition depends on fatty acid oxidation, is coupled to decreased glucose oxidation and operates both during normo- and hyperglycemia.

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Metadata

Authors
SAKO, Y., & GRILL, V. E.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
1990-10
Volume
127
Issue
4
Pages
1580-1589
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo-127-4-1580
OpenAlex
W2017783641
Cited by
374
References
4
FWCI
5.90
Type
journal article
Language
en
Open access
closed

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