The effect of an antilipolytic agent (acipimox) on the insulin resistance of lipid and glucose metabolism in hypertriglyceridaemic patients.
Hypertriglyceridaemia is associated with insulin resistance of both lipid and glucose metabolism. It is not known whether the insulin resistance affects both glucose oxidation and glycogen formation. To study the oxidative and non-oxidative pathways of non-esterified fatty acids (NEFA) and glucose metabolism, eight male hypertriglyceridaemic subjects were studied during insulin infusion (75 and 340 pmol/m2.min) in combination with indirect calorimetry and infusions of [3-3H]glucose and [1-14C]palmitate before and after 4 weeks of treatment with the antilipolytic agent acipimox (250 mg three times daily). Compared with eight healthy subjects the hypertriglyceridaemic subjects were resistant to the antilipolytic effect of insulin, both in the basal state (P < 0.05) and during insulin infusion (P < 0.05). This was associated with impaired insulin-stimulated glucose uptake (P < 0.05), predominantly in the non-oxidative pathway (P < 0.05). Acipimox decreased basal NEFA concentrations (P < 0.01) and reduced lipid oxidation during low-dose insulin infusion (P < 0.05). Glucose uptake, predominantly glycogen formation, was stimulated by acipimox (P < 0.05). In conclusion, the insulin resistance of glucose metabolism associated with hypertriglyceridaemia is largely due to a defect in non-oxidative glucose metabolism. Acipimox improves glucose metabolism both by affecting glucose oxidation (low-dose insulin) and non-oxidative glucose metabolism (high-dose insulin).
Saloranta
C
C
Fourth Department of Medicine, Helsinki University Hospital, Finland.
Groop
L
L
Ekstrand
A
A
Franssila-Kallunki
A
A
Taskinen
M R
MR
D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010168:Palmitates / Q000008:administration & dosage / Q000494:pharmacology; D011719:Pyrazines / Q000627:therapeutic use*
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D010168:Palmitates; D011719:Pyrazines; D005947:Glucose; C027696:acipimox