Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes.
OBJECTIVE
Overproduction of intestinally derived apoB-48-containing triglyceride-rich lipoproteins (TRLs) (chylomicrons) has recently been described in type 2 diabetes, as is known for hepatic TRL-apoB-100 (very-low-density lipoprotein) production. Furthermore, insulin acutely inhibits both intestinal and hepatic TRL production, whereas this acute inhibitory effect on very-low-density lipoprotein production is blunted in type 2 diabetes. It is not currently known whether this acute effect on chylomicron production is similarly blunted in humans with type 2 diabetes.


RESULTS
We investigated the effect of acute hyperinsulinemia on TRL metabolism in 18 type 2 diabetic men using stable isotope methodology. Each subject underwent 1 control (saline infusion [SAL]) lipoprotein turnover study followed by a second study, under 1 of the 3 following clamp conditions: (1) hyperinsulinemic-euglycemic, (2) hyperinsulinemic-hyperglycemic, or (3) hyperinsulinemic-euglycemic plus intralipid and heparin. TRL-apoB-48 and TRL-apoB-100 production and clearance rates were not different between SAL and clamp and between the different clamp conditions, except for significantly lower TRL-apoB-100 clearance and production rates in hyperinsulinemic-euglycemic plus intralipid and heparin clamp compared with SAL.


CONCLUSIONS
This is the first demonstration in individuals with type 2 diabetes that chylomicron production is resistant to the normal acute suppressive effect of insulin. This phenomenon may contribute to the highly prevalent dyslipidemia of type 2 diabetes and potentially to atherosclerosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00950209.
Unité Mixte de Recherche Institut National de la Recherche Agronomique, University of la Méditerranée, Marseille, France.
Juan-Patricio
JP
Nogueira
Marie
M
Maraninchi
Sophie
S
Béliard
Nadège
N
Padilla
Laurence
L
Duvillard
Julien
J
Mancini
Alain
A
Nicolay
Changting
C
Xiao
Bernard
B
Vialettes
Gary F
GF
Lewis
René
R
Valéro
D053299:Apolipoprotein B-100 / Q000097:blood; D053283:Apolipoprotein B-48 / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002914:Chylomicrons / Q000097:blood*; D048909:Diabetes Complications / Q000097:blood / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology; D004655:Emulsions / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005602:France; D015309:Glucose Clamp Technique; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010743:Phospholipids / Q000008:administration & dosage; D013024:Soybean Oil / Q000008:administration & dosage; D013997:Time Factors
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001786:Blood Glucose; D002914:Chylomicrons; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D006493:Heparin