title: Down-regulation of pyruvate dehydrogenase phosphatase in obese subjects is a defect that signals insulin resistance.
abstract: OBJECTIVE
  The objective of this study was to determine whether down-regulation of pyruvate dehydrogenase phosphatase (PDP) is responsible for poorly active pyruvate dehydrogenase (PDH) in circulating lymphocytes (CLs) of obese subjects (ObS), and if so, whether it improves when their plasma insulin rises.
  
  
  METHODS
  PDH activity was compared in lysed CLs of 10 euglycemic ObS and 10 sex- and age-matched controls before and during plasma insulin enhancement in an oral glucose tolerance test. It was evaluated without (PDHa) or with Mg/Ca or Mg at various concentrations to assess PDP1 or PDP2 activities or with Mg/Ca and exogenous PDP to determine total PDH activity (PDHt), which is an indirect measure of the amount of PDH. The insulin sensitivity index was calculated, and PDP1 and PDP2 mRNA was sought in the CLs.
  
  
  RESULTS
  At T0 in ObS, PDHt was normal, whereas PDHa and PDP1 activity was below normal at all Mg/Ca concentrations. PDP2 activity was undetectable in both groups. PDP1 and PDP2 mRNA was identified, and insulin sensitivity index and PDHa were directly correlated. During the oral glucose tolerance test, plasma insulin rose considerably more in ObS than in controls; PDHa and PDP1 activity also increased but remained significantly below normal, and PDHt was unvaried in both groups.
  
  
  CONCLUSIONS
  PDP1 is down-regulated in CLs of ObS because it is poorly sensitive to Mg/Ca; this defect is attenuated when plasma insulin is greatly enhanced.
authors.affiliation: Dipartment of Medicine, Section of Biochemistry, University of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccinini
authors.forename: Michael
authors.initials: M
authors.lastname: Mostert
authors.forename: Gianfrancesco
authors.initials: G
authors.lastname: Alberto
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramondetti
authors.forename: Rosa F
authors.initials: RF
authors.lastname: Novi
authors.forename: Paola
authors.initials: P
authors.lastname: Dalmasso
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rinaudo
mesh_terms: D000328:Adult; D002136:Calcium, Dietary / Q000008:administration & dosage; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008214:Lymphocytes / Q000201:enzymology; D008274:Magnesium / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology*; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D002136:Calcium, Dietary; D007328:Insulin; D012333:RNA, Messenger; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D008274:Magnesium