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Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production.

Abstract：

:In healthy individuals, peripheral insulin resistance evoked by dietary saturated lipid can be accompanied by increased insulin secretion such that glucose tolerance is maintained. Substitution of long-chain omega-3 fatty acids for a small percentage of dietary saturated fat prevents insulin resistance in response to high-saturated fat feeding. We substituted a small amount (7%) of dietary lipid with long-chain omega-3 fatty acids during 4 wk of high-saturated fat feeding to investigate the relationship between amelioration of insulin resistance and glucose-stimulated insulin secretion (GSIS). We demonstrate that, despite dietary delivery of saturated fat throughout, this manipulation prevents high-saturated fat feeding-induced insulin resistance with respect to peripheral glucose disposal and reverses insulin hypersecretion in response to glucose in vivo. Effects of long-chain omega-3 fatty acid enrichment to lower GSIS were also observed in perifused islets suggesting a direct effect on islet function. However, long-chain omega-3 fatty acid enrichment led to hepatic insulin resistance with respect to suppression of glucose output and impaired glucose tolerance in vivo. Our data demonstrate that the insulin response to glucose is suppressed to a greater extent than whole-body insulin sensitivity is enhanced by enrichment of a high-saturated fat diet with long-chain omega-3 fatty acids. Additionally, reduced GSIS despite glucose intolerance suggests that either long-chain omega-3 fatty acids directly impair the beta-cell response to saturated fat such that insulin secretion cannot be augmented to normalize glucose tolerance or beta-cell compensatory hypersecretion represents a response to insulin resistance at the level of peripheral glucose disposal but not endogenous glucose production.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Holness MJ,Greenwood GK,Smith ND,Sugden MC

doi

10.1210/en.2003-0479

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

3958-68

issue

eissn

0013-7227

issn

1945-7170

journal_volume

144

pub_type

杂志文章

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Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production.