title: Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM.
abstract: Insulin administration to healthy subjects inhibits the production of very low density lipoprotein (VLDL)1 (Svedbergs flotation (Sf) rate 60-400) without affecting that of VLDL2 (Sf 20-60) sub-class. This study was designed to test whether this hormonal action is impaired in non-insulin-dependent diabetes mellitus (NIDDM). We studied six men with NIDDM (age 53 +/- 3 years, body mass index 27.0 +/- 1.0 kg/m2, plasma triglycerides 1.89 +/- 0.22 mmol/l) during an 8.5 h infusion of saline (control) and then in hyperinsulinaemic (serum insulin approximately 540 pmol/l) conditions during 8.5 h infusions of glucose and insulin to give either hyper- and normoglycaemic conditions. [3-2H]-leucine was used as tracer and kinetic constants derived using a non-steady-state multicompartmental model. Compared to the control study, patients with NIDDM reduced VLDL1 apo B production by only 3 +/- 8% after 8.5 h of hyperinsulinaemia (701 +/- 102 vs 672 +/- 94 mg/day respectively, NS) in hyperglycaemic conditions and by 9 +/- 21% under normoglycaemic conditions (603 +/- 145 mg/day). In contrast, in normal subjects insulin induced a 50 +/- 15% decrement in VLDL1 apo B production (p < 0.05). Direct synthesis of VLDL2 apo B in patients with NIDDM was not markedly affected by insulin. We conclude that a contributory factor to hypertriglyceridaemia in NIDDM is the inability of insulin to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum nonesterfied fatty acids.
authors.affiliation: Department of Medicine, University of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Malmström
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: M
authors.initials: M
authors.lastname: Caslake
authors.forename: D
authors.initials: D
authors.lastname: Bedford
authors.forename: P
authors.initials: P
authors.lastname: Stewart
authors.forename: H
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003903:Deuterium; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D014280:Triglycerides / Q000097:blood*
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D003903:Deuterium; D007930:Leucine