title: Insulin receptor exon 11+/- is expressed in Zucker (fa/fa) rats, and chlorogenic acid modifies their plasma insulin and liver protein and DNA.
abstract: In vivo studies confirmed that chlorogenic acid (CGA) improved glucose tolerance and mineral pool distribution in obese Zucker (fa/fa) rats. We found a significant decrease (P<.05) in postprandial blood glucose concentrations, which may have been due to an improved sensitivity to insulin. Impaired glucose tolerance and insulin resistance have been associated with differences in the hepatic mRNA expression of the spliced variants of the insulin receptor at exon 11. Spliced variants of the insulin receptor have not been studied in obese Zucker (fa/fa) rats, and no information exists about the effects of CGA in vivo as a possible insulin sensitizer. Thus, we studied the in vivo effect of CGA on plasma insulin concentrations during a glucose tolerance test, liver protein and DNA concentrations, the hepatic activity of glucose-6-phosphatase (G-6-PASE) and the mRNA expression of the two variants of the insulin receptor at exon 11. Zucker (fa/fa) rats were implanted with jugular vein catheters. Chlorogenic acid was administered (5 mg/kg body weight per day) for 3 weeks via intravenous infusion. In the CGA-treated group, areas under the curve (AUC) for blood glucose and plasma insulin improved (P<.005), and the protein and DNA concentrations in the liver increased (P<.05). No significant differences (P>.05) were found between groups for the hepatic G-6-PASE activity. The insulin receptor exon 11(+) and the exon 11(-) variants were expressed in the liver of Zucker (fa/fa) rats without significant changes (P>.05). Chlorogenic acid improved some cellular mechanisms that are stimulated by insulin.
authors.affiliation: Department of Chemistry, Minnesota State University, Mankato, 56001, USA.
authors.forename: Delcy V
authors.initials: DV
authors.lastname: Rodriguez de Sotillo
authors.forename: Mary
authors.initials: M
authors.lastname: Hadley
authors.forename: Julio E
authors.initials: JE
authors.lastname: Sotillo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000032:analysis*; D005951:Glucose Tolerance Test; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D002726:Chlorogenic Acid; D004247:DNA; D011972:Receptor, Insulin; C023553:mannose-6-phosphatase; D010744:Phosphoric Monoester Hydrolases; D005952:Glucose-6-Phosphatase