Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans

J Clin Endocrinol Metab. 2011 Aug;96(8):2519-24. doi: 10.1210/jc.2011-0266. Epub 2011 May 18.


Context: The incretin effect is responsible for the higher insulin response to oral glucose than to iv glucose at matching glucose levels. It is not known whether this effect is restricted to glucose only.

Objective: The aim of the study was to examine whether insulin and incretin hormone responses are higher after oral vs. iv challenge of a lipid emulsion with matching triglyceride levels in humans.

Design, settings, and participants: A lipid emulsion (Intralipid) was administered orally (3 ml/kg) or iv (variable infusion rates to match triglyceride levels after oral ingestion) in healthy lean males (n = 12) at a University Clinical Research Unit. Samples were collected during 300 min.

Main outcome measures: We measured the suprabasal area under the curve for insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and the insulin secretory rate based on C-peptide levels by deconvolution.

Results: Triglyceride levels increased similarly after oral and iv lipid; also, glucose and free fatty acid levels were similar in the two tests. Oral lipid elicited a clear insulin and C-peptide response, whereas no insulin or C-peptide responses were observed during iv lipid. Total and intact GIP and GLP-1 levels both increased after oral lipid administration but were not significantly altered after iv lipid.

Conclusions: At matching triglyceride levels and with no difference in glucose and free fatty acid levels, oral lipid ingestion but not iv lipid infusion elicits a clear insulin response in association with increased GIP and GLP-1 concentrations. This may suggest that the incretin hormones also contribute to the islet response to noncarbohydrate nutrients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Emulsions / administration & dosage
  • Fatty Acids, Nonesterified / blood
  • Gastric Inhibitory Polypeptide / blood
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Incretins / blood*
  • Incretins / metabolism*
  • Infusions, Intravenous
  • Insulin / blood*
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Phospholipids / administration & dosage*
  • Soybean Oil / administration & dosage*
  • Triglycerides / blood
  • Young Adult


  • Blood Glucose
  • C-Peptide
  • Emulsions
  • Fatty Acids, Nonesterified
  • Incretins
  • Insulin
  • Phospholipids
  • Triglycerides
  • soybean oil, phospholipid emulsion
  • Gastric Inhibitory Polypeptide
  • Soybean Oil
  • Glucagon-Like Peptide 1