Document Detail


The role of insulin and proinsulin in the regulation of triglyceride metabolism.
MedLine Citation:
PMID:  9288540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanisms underlying the associations between abnormal glucose tolerance and myocardial infarction are poorly understood. It has often been suggested that an increased plasma insulin concentration is causally linked to many of the metabolic abnormalities that are associated with abnormal glucose tolerance, although this suggestion remains controversial. Recently it has been proposed that proinsulin and proinsulin-like molecules may also be involved in the atherogenic process. Both hyperinsulinaemia and insulin resistance are associated with fasting hypertriglyceridaemia and both increased VLDL production and increased plasma triglyceride concentrations commonly occur in association with abnormal glucose tolerance and atheromatous vascular disease. In order to study the effects of insulin, proinsulin and proinsulin-like molecules on hepatic triglyceride secretion we have undertaken experiments in vitro using the liver cell line HepG2. In conjunction with these in vitro experiments we have also studied, in vivo, the associations between insulin, proinsulin, proinsulin-like molecules and plasma triglyceride concentrations in subjects with both normal and abnormal glucose tolerance. Our results in vitro show that proinsulin and proinsulin-like molecules have similar and not different effects to insulin but are less biologically active. In vivo, our results show that concentrations of insulin, proinsulin and proinsulin-like molecules per se are not an important determinant of plasma triglyceride concentrations. Both abnormal NEFA suppression during an oral glucose tolerance test and increased central adiposity are closely linked to poor glucose tolerance and are the most important determinants of plasma triglyceride concentrations. Taken together these results suggest that it is not insulin nor proinsulin concentrations per se that are causally linked to hypertriglyceridaemia. We suggest that abnormal NEFA suppression plays an important part in the increase in risk of vascular disease associated with insulin resistance.
Authors:
C D Byrne; N J Wareham; C N Hales
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association     Volume:  105 Suppl 2     ISSN:  0947-7349     ISO Abbreviation:  Exp. Clin. Endocrinol. Diabetes     Publication Date:  1997  
Date Detail:
Created Date:  1997-10-16     Completed Date:  1997-10-16     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9505926     Medline TA:  Exp Clin Endocrinol Diabetes     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  29-35     Citation Subset:  IM    
Affiliation:
University Dept of Clinical Biochemistry, Addenbrookes Hospital, Cambridge. cdtb@mole.bio.cam.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Carcinoma, Hepatocellular
Diabetes Mellitus, Type 2 / blood*
Fatty Acids, Nonesterified / blood
Female
Glucose Tolerance Test
Humans
Insulin / blood,  pharmacology,  physiology*
Lipolysis / drug effects*
Liver Neoplasms
Male
Middle Aged
Proinsulin / blood,  pharmacology,  physiology*
Reference Values
Regression Analysis
Sex Characteristics
Triglycerides / blood,  metabolism*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Triglycerides; 11061-68-0/Insulin; 9035-68-1/Proinsulin

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


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