J. Lipid Mediators Cell Signalling 17 (1997) 97–113 Plasma PAF acetylhydrolase in non-insulin dependent diabetes mellitus and obesity: effect of hyperinsulinemia and lovastatin treatment George B. Kudolo a, *, Peter Bressler b , Ralph A. DeFronzo c a Department of Clinical Laboratory Sciences, School of Allied Health Sciences, Uniersity of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drie, San Antonio, TX 78284 -7772, USA b Endocrine and Diabetes Associates of Texas, Dallas, TX 75230, USA c Department of M edicine /Diabetes Diision, Uniersity of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drie, San Antonio, TX 78284 -7772, USA Received 16 March 1997; received in revised form 31 July 1997; accepted 31 July 1997 Abstract Insulin resistance is characterized principally by impaired insulin-mediated glucose uptake which provokes a compensatory increase in pancreatic -cell secretory activity. For a time this may produce well-controlled plasma glucose levels but as the insulin resistance worsens the augmented insulin production becomes inadequate to keep plasma glucose at euglycemia leading to the development of non-insulin dependent diabetes mellitus (NIDDM), accompa- nied by hyperinsulinemia and hyperglycemia. A number of metabolic defects are associated with NIDDM including obesity, hypercoagulability, cardiovascular disease risk factors such as hypertension and dyslipidemia and these constitute the insulin resistance syndrome. The identity of the biochemical factor that might link all these defects is not yet known. We have hypothsisized that platelet-activating factor (1-O -alkyl-2-acetyl-sn -glycero-3-phosphocholine, PAF) may be such a link. In this study, we measured plasma acetylhydrolase (EC.1.1.48), which degrades PAF to the inactive metabolise lyso-PAF, as a surrogate for PAF activity in three groups of hypercholesterolemic subjects: lean controls (n =9), non-diabetic obese (n =6) and NIDDM subjects (n =6). The ages and body mass indices of the subjects were 46 3.1 and 24.2 2.2 for the lean controls, 52 2.5 and 28.7 0.9 for the NIDDM * Corresponding author. 0929-7855/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PII S0929-7855(97)00023-0