Document Detail


Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients.
MedLine Citation:
PMID:  19417125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [(2)H(5)]glycerol rate of appearance (R(a))] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and beta-hydroxybutyrate, and a decreased suppression of glycerol R(a) (P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced (P = 0.05 and P < 0.04, respectively), and glycerol R(a) was more suppressed [-40 (137) vs. +7 (202) mumol/min of placebo, P < 0.05] despite a greater fall in insulin [-85 (176) vs. -20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis.
Authors:
Amalia Gastaldelli; Arturo Casolaro; Demetrio Ciociaro; Silvia Frascerra; Monica Nannipieri; Emma Buzzigoli; Ele Ferrannini
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-05-05
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  297     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-08-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E225-30     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antilipemic Agents / pharmacology,  therapeutic use
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism*
Double-Blind Method
Fasting / blood,  metabolism
Fatty Acids, Nonesterified / blood,  metabolism
Female
Glycerol / blood,  metabolism
Humans
Insulin / blood,  metabolism
Lipolysis / drug effects*
Male
Middle Aged
Placebos
Thiazolidinediones / pharmacology*,  therapeutic use*
Triglycerides / blood,  metabolism
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 0/Fatty Acids, Nonesterified; 0/Placebos; 0/Thiazolidinediones; 0/Triglycerides; 11061-68-0/Insulin; 111025-46-8/pioglitazone; 56-81-5/Glycerol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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