title: Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.
abstract: BACKGROUND
  Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism.
  
  
  METHODS
  Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo-controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed.
  
  
  RESULTS
  Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome.
  
  
  CONCLUSIONS
  Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam, Nuthetal, Germany - rudovich@dife.de.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rudovich
authors.forename: Olga
authors.initials: O
authors.lastname: Pivovarova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bernigau
authors.forename: Andrea
authors.initials: A
authors.lastname: Sparwasser
authors.forename: Christopher
authors.initials: C
authors.lastname: Tacke
authors.forename: Veronica
authors.initials: V
authors.lastname: Murahovshi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mertes
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Birkenfeld
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Pfeiffer
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004311:Double-Blind Method; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D014660:Vasoactive Intestinal Peptide / Q000097:blood*
chemical_list: D002316:Cardiotonic Agents; D016326:Extracellular Matrix Proteins; D007328:Insulin; D014660:Vasoactive Intestinal Peptide; D020909:Acarbose