Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments.
Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins involved in nutritional regulation. Metformin and pioglitazone improve insulin sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and expression were determined. Serum DPP-IV activity increased whereas tissue activity decreased as the rats aged. Treatment of rats with metformin, pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or kidney. Metformin and pioglitazone significantly (P<0.05) reduced serum DPP-IV activity and glycosylated hemoglobin. Glyburide did not lower DPP-IV activity or glycosylated hemoglobin. Regression analysis showed serum DPP-IV activity correlated with glycosylated hemoglobin (r=0.92) and glucagon-like peptide-1 levels (r=-0.49). Metformin, pioglitazone, and glyburide had no effect on serum DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors. We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.
Lenhard
James M
JM
Department of Metabolic Diseases, GlaxoSmithKline Inc., Research Triangle Park, NC 27709, USA. jimlenhard@hotmail.com <jimlenhard@hotmail.com>
Croom
Dallas K
DK
Minnick
Dana T
DT
D000375:Aging / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000008:administration & dosage / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D000077205:Pioglitazone; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000378:metabolism*
D001786:Blood Glucose; D006454:Hemoglobins; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D010446:Peptide Fragments; D011498:Protein Precursors; D045162:Thiazolidinediones; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008687:Metformin; D018819:Dipeptidyl Peptidase 4; D005905:Glyburide; D000077205:Pioglitazone