Diabetologia

, Volume 40, Issue 9, pp 1018–1027

Chronic effect of fatty acids on insulin release is not through the alteration of glucose metabolism in a pancreatic beta-cell line (βHC9)

  • Y. Liang
  • C. Buettger
  • D. K. Berner
  • F. M. Matschinsky

DOI: 10.1007/s001250050783

Cite this article as:
Liang, Y., Buettger, C., Berner, D. et al. Diabetologia (1997) 40: 1018. doi:10.1007/s001250050783

Summary

Hyperinsulinaemia in the fasting state and a blunted insulin secretory response to acute glucose stimulation are commonly observed in obesity associated non-insulin-dependent diabetes mellitus. Hyperlipidaemia is a hallmark of obesity and may play a role in the pathogenesis of this beta-cell dysfunction because glucose metabolism in pancreatic beta cells may be altered by the increased lipid load. We tested this hypothesis by assessing the chronic effect of oleic acid on glucose metabolism and its relationship with glucose-induced insulin release in βHC9 cells in tissue culture. Our results show: (1) A 4-day treatment with oleic acid caused an enhancement of insulin release at 0–5 mmol/l glucose concentrations while a significant decrease in insulin release occurred when the glucose level was greater than 15 nmol/l; (2) Hexokinase activity was increased and a corresponding left shift of the dose-dependency curve of glucose usage was observed associated with inhibition of glucose oxidation in oleic acid treated βHC9 cells, yet the presumed glucose-related ATP generation did not parallel the change in insulin release due to glucose; (3) The rate of cellular respiration was markedly increased in oleic acid treated βHC9 cells both in the absence of glucose and at all glucose concentrations tested. This enhanced oxidative metabolism may explain the increased insulin release at a low glucose level but is clearly dissociated from the blunted insulin secretion at high glucose concentrations. We conclude that a reduction of oxidative metabolism in pancreatic beta cells is unlikely to be the cause of the dramatic effect that high levels of non-esterified fatty acids have on glucose-induced insulin release. [Diabetologia (1997) 40: 1018–1027]

Keywords Islet of LangerhanslipotoxicityβHC9 cellsglucose metabolism
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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Y. Liang
    • 1
  • C. Buettger
    • 2
  • D. K. Berner
    • 2
  • F. M. Matschinsky
    • 1
  1. 1.Department of Biochemistry and Biophysics, University of Pensylvania School of Medicine, Philadelphia, Pennsylvania, USAUS
  2. 2.Diabetes Research Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USAUS
  3. 3.Ergoscience, Charlestown, Massachusetts, USAUS