Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes

Am J Respir Crit Care Med. 2001 Mar;163(4):840-6. doi: 10.1164/ajrccm.163.4.9912132.


To determine the influence of glucagon-like peptides on the secretion of human pulmonary surfactant, we used human type II pneumocytes. In these cells, GLP-1(7-36) amide and exendin-4 stimulated phosphatidylcholine secretion (PC) and cAMP formation in a concentration-dependent manner; these effects were reversed by exendin(9-39). No changes were observed with other related peptides. The mechanism by which GLP-1(7-36) amide exerts its stimulatory effect was investigated with various agents that are well known to be stimulators or inhibitors of PC secretion. Thus, 8-bromo-cAMP increased and both Rp-cAMPS and H-89, the latter an inhibitor of protein kinase A (PKA), reduced pulmonary surfactant secretion in type II pneumocytes. Also, GLP-1(7-36) amide and TPA exerted additive effects in stimulating PC secretion, and Calph C, a potent inhibitor of protein kinase C (PKC), blocked most of the effect of GLP-1(7-36) amide. By contrast, both the calcium ionophore A23187 and GLP-1(7-36) amide had additive effects in increasing PC secretion, and the specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase (Ca-CM-PK), KN-62, inhibited the effect of A23187 but did not alter the stimulatory action of GLP-1(7-36) amide. Our findings suggest that both PKA and PKC are involved in the stimulatory effects of GLP-1(7-36) amide on PC secretion, whereas this peptide has no effect on PC secretion through a Ca-CM-PK mechanism.

Publication types

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

MeSH terms

  • Adult
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Humans
  • Lung / cytology
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Phosphatidylcholines / analysis
  • Pulmonary Surfactants / drug effects
  • Pulmonary Surfactants / metabolism*
  • Reference Values
  • Sensitivity and Specificity


  • Peptide Fragments
  • Phosphatidylcholines
  • Pulmonary Surfactants
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon