Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms

J Med Food. 2016 Sep;19(9):836-43. doi: 10.1089/jmf.2016.3711. Epub 2016 Aug 19.


The aim of this study was to evaluate the antidiabetic properties of collagen hydrolysates (CHs). CHs exhibited dipeptidyl peptidase-IV inhibitory activity and stimulated glucagon-like-peptide-1 (GLP-1) secretion in vitro. We also determined whether CHs improve glucose tolerance in normal mice. Oral administration of CHs suppressed the glycemic response during the oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT), but the effects were weaker in IPGTT than in OGTT. CHs had no effect on the gastric emptying rate. A pretreatment with the GLP-1 receptor antagonist, exendin 9-39 (Ex9), partially reversed the glucose-lowering effects of CHs, but only when coadministered with glucose. CHs administered 45 min before the glucose load potentiated the glucose-stimulated insulin secretion. This potentiating effect on insulin secretion was not reversed by the pretreatment with Ex9, it appeared to be enhanced. These results suggest that CHs improve glucose tolerance by inhibiting intestinal glucose uptake and enhancing insulin secretion, and also demonstrated that GLP-1 was partially involved in the inhibition of glucose uptake, but not essential for the enhancement of insulin secretion.

Keywords: DPP-IV; blood glucose; collagen peptides; diabetes; dietary supplements; functional foods; insulin; intestinal glucose uptake.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / metabolism*
  • Cichlids
  • Collagen / pharmacology*
  • Collagen / therapeutic use
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Fish Proteins / pharmacology*
  • Fish Proteins / therapeutic use
  • Glucagon-Like Peptide 1 / blood*
  • Glucose Intolerance / blood*
  • Glucose Intolerance / drug therapy
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin Secretion
  • Intestinal Absorption / drug effects
  • Male
  • Mice, Inbred C57BL
  • Protein Hydrolysates / pharmacology*
  • Protein Hydrolysates / therapeutic use
  • Reference Values


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Fish Proteins
  • Hypoglycemic Agents
  • Insulin
  • Protein Hydrolysates
  • Glucagon-Like Peptide 1
  • Collagen
  • Dipeptidyl Peptidase 4