Insulinotropin PACAP potentiates insulin action. Stimulation of glucose uptake in 3T3-LI adipocytes.
PAC1 receptor was expressed in the rat fat tissue and 3T3-L1 adipocytes. PACAP-38 (10 nM) significantly enhanced insulin induced 2-deoxyglucose uptake by 3T3-L1 adipocytes. GLP-1 has a similar effect. PACAP-38 further increased insulin stimulated phosphatidylinositol (PI) 3-kinase activity, but has not effect on tyrosine phosphorylation of insulin receptor beta-subunit or IRS-1. These results reveal that PACAP-38 enhances insulin induced glucose uptake, an effect probably mediated by PI 3-kinase. In conclusion, PACAP potentiates not only insulin secretion but also insulin action in adipocytes, thereby exhibiting antidiabetic actions at two important steps of glucose metabolism (Fig. 2).
Yada
T
T
Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. tyada@jichi.ac.jp
Nakata
M
M
Shioda
S
S
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004357:Drug Synergism; D005934:Glucagon / Q000008:administration & dosage; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage*; D051379:Mice; D008954:Models, Biological; D009479:Neuropeptides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors / Q000008:administration & dosage; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000378:metabolism
C495402:Adcyap1 protein, mouse; C495504:Adcyap1r1 protein, mouse; D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D003847:Deoxyglucose; D005947:Glucose