A fatty acid-dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion

Robert L. Dobbins, Michael W. Chester, Brent E. Stevenson, Murphy B. Daniels, Daniel T. Stein, J. Denis McGarry

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic acid (NA) caused essentially complete ablation of insulin secretion (IS) in response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide (as previously found using glucose as the β-cell stimulus). However, in all cases, IS became supranormal when a high FFA level was maintained by co-infusion of lard oil plus heparin. Each of these secretagogues elicited little, if any, IS from the isolated, perfused 'fasted' pancreas when tested simply on the background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate was also included in the medium. Similarly, IS from the perfused pancreas, in response to depolarizing concentrations of KCl, was markedly potentiated by palmitate. As was the case with intravenous glucose adminstration, fed animals produced an equally robust insulin response to glibenclamide regardless of whether their low basal FFA concentration was further reduced by NA. In the fasted state, arginine-induced glucagon secretion appeared to be independent of the prevailing FFA concentration. The findings establish that the essential role of circulating FFA for glucose-stimulated IS after food deprivation also applies in the case of nonglucose secretagogues. In addition, they imply that (i) a fatty acid-derived lipid moiety, which plays a pivotal role in IS, is lost from the pancreatic β-cell during fasting; (ii) in the fasted state, the elevated level of plasma FFA compensates for this deficit; and (iii) the lipid factor acts at a late step in the insulin secretory pathway that is common to the action of a wide variety of secretagogues.

Original languageEnglish (US)
Pages (from-to)2370-2376
Number of pages7
JournalJournal of Clinical Investigation
Issue number11
StatePublished - Jun 1 1998
Externally publishedYes


  • Fatty acids
  • Insulin secretagogues
  • Insulin secretion

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'A fatty acid-dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion'. Together they form a unique fingerprint.

Cite this