Send to

Choose Destination
See comment in PubMed Commons below
Am J Physiol. 1999 Jun;276(6 Pt 1):E1055-66.

Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation.

Author information

  • 1Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5G 2C4.


The in vivo effect of elevated free fatty acids (FFA) on beta-cell function in humans remains extremely controversial. We examined, in healthy young men, the acute (90 min) and chronic (48 h) effects of an approximately twofold elevation of plasma FFA vs. control on glucose-stimulated insulin secretion (GSIS). GSIS was studied in response to a graded intravenous glucose infusion (peak plasma glucose, approximately 10 mmol/l, n = 8) and a two-step hyperglycemic clamp (10 and 20 mmol/l, n = 8). In the acute studies, GSIS was significantly higher, insulin sensitivity index (SI) was lower, and disposition index (DI = insulin sensitivity x insulin secretion) was unchanged with elevated FFA vs. control [2-step clamp: DI = 8.9 +/- 1.4 x 10(-3) l2. kg-1. min-2 in control vs. 10.0 +/- 1.9 x 10(-3) l2. kg-1. min-2 with high FFA, P = nonsignificant (NS)]. In the chronic studies, there was no difference in absolute GSIS between control and high FFA studies, but there was a reduction in SI and a loss of the expected compensatory increase in insulin secretion as assessed by the DI (2-step clamp: DI = 10.0 +/- 1.2 x 10(-3) l2. kg-1. min-2 in control vs. 6.1 +/- 0.7 x 10(-3) l2. kg-1. min-2 with high FFA, P = 0.01). In summary, 1) acute and chronic FFA elevation induces insulin resistance; 2) with acute FFA elevation, this insulin resistance is precisely countered by an FFA-induced increase in insulin secretion, such that DI does not change; and 3) chronic FFA elevation disables this beta-cell compensation.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center