Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus.

Abstract

To determine the therapeutic effect of the carinitine palmitoyltransferase I (CPT-I) inhibitor, etomoxir, eight hospitalized obese non-insulin-dependent diabetes mellitus (NIDDM) patients were studied (body mass index [BMI], 28.7 +/- 1.3 kg/m2; age, 54 +/- 8 years [means +/- SE]) at baseline (placebo = t1), and after oral etomoxir (50 mg/d = t2, 100 mg = 3, 150 mg = t4, 200 mg = t5, placebo = t6). Fasting blood glucose (mmol/L), triglycerides (mmol/L), cholesterol (mmol/L), free fatty acids (mumol/L), beta-hydroxybutyrate (mumol/L), and alanine aminotransferase (GPT, U/L) were determined (t1 to t6), as were glucose utilization (M value; indirect calorimetry) and hepatic glucose production during a 10 mU/kg.min euglycemic clamp (t1 and t4). A dose-dependent decrease was induced by etomoxir in fasting blood glucose (t1 to t5: 9.5 +/- 0.7, 8.7 +/- 1.0, 8.3 +/- 1.1 [P v t1 less than .05], 7.8 +/- 0.9, [P v t1 less than .01], 7.9 +/- 1.1 [P v t1 less than .05]), which was reversible in t6 (9.9 +/- 1.1). Mean plasma lipids were reduced (t1 v t5) for triglycerides (-54%, P v t1 less than .01), cholesterol (-24%, P v t1 less than .05), and beta-hydroxybutyrate (-44%, P v t2 less than .01), while free fatty acids increased by 52% (P v t1 less than .05), as did GPT (t1: 17 +/- 3; t5: 32 +/- 7 U/L [P v t1 less than .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: K Ratheiser, B Schneeweiss, W Waldhäusl, P Fasching, A Korn, P Nowotny, M Rohac, H P Wolf
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 40 Issue 11 Pg. 1185-90 (Nov 1991) ISSN: 0026-0495 [Print] United States
• PMID: 1943747 (Publication Type: Journal Article)

Chemical References

• Epoxy Compounds
• Fatty Acids, Nonesterified
• Hydroxybutyrates
• Hypoglycemic Agents
• Lactates
• Lipids
• Triglycerides
• Lactic Acid
• Cholesterol
• Carnitine O-Palmitoyltransferase
• Alanine Transaminase
• Glucose
• etomoxir
• 3-Hydroxybutyric Acid

Topics

• 3-Hydroxybutyric Acid
• Adult
• Alanine Transaminase (blood)
• Carnitine O-Palmitoyltransferase (antagonists & inhibitors)
• Cholesterol (blood)
• Diabetes Mellitus, Type 2 (metabolism)
• Dose-Response Relationship, Drug
• Epoxy Compounds (pharmacology)
• Fatty Acids, Nonesterified (blood)
• Glucose (biosynthesis)
• Glucose Clamp Technique
• Humans
• Hydroxybutyrates (blood)
• Hypoglycemic Agents (pharmacology)
• Lactates (blood)
• Lactic Acid
• Lipids (blood)
• Liver (metabolism)
• Middle Aged
• Triglycerides (blood)