Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes.
To study whether therapeutic reduction of non-esterified fatty acids (NEFA) can be used to improve glucose metabolism, we administered the antilipolytic agent, acipimox, 250 mg four times daily for 4 weeks in eight obese Type 2 diabetic patients. Glucose and NEFA metabolism were assessed before and after treatment with a two-step euglycaemic hyperinsulinaemic clamp (0.25 and 1 mU kg-1 min-1 insulin) combined with infusions of [3-3H] glucose and [1-14C] palmitate. Three days of acipimox treatment reduced 24-h serum NEFA levels by 10%, but the difference disappeared after 4 weeks of treatment mainly due to a two-fold rise in morning NEFA concentrations (p < 0.01). After 3 days of acipimox treatment, fasting and 24-h plasma glucose and serum triglyceride concentrations were significantly reduced (p < 0.05), but no longer after 4 weeks of treatment. Despite the rebound rise in NEFA, acute administration of acipimox still inhibited both oxidative and non-oxidative NEFA metabolism in the basal state (p < 0.01-0.001) and during insulin infusion (p < 0.05-0.001). Inhibition of NEFA metabolism was associated with increased insulin-stimulated glucose uptake (from 3.56 +/- 0.28 to 5.14 +/- 0.67 mumol kg-1 min-1, p < 0.05), mainly due to stimulation of non-oxidative glucose disposal (from 1.74 +/- 0.23 to 3.03 +/- 0.53 mumol kg-1 min-1, p < 0.05). In conclusion, acipimox administered acutely inhibits NEFA appearance (lipolysis), which is associated with improved glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Saloranta
C
C
Third Department of Medicine, Helsinki University Hospital, Finland.
Groop
L
L
Ekstrand
A
A
Franssila-Kallunki
A
A
Eriksson
J
J
Taskinen
M R
MR
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D011719:Pyrazines; D014280:Triglycerides; D002784:Cholesterol; D005947:Glucose; C027696:acipimox; D005990:Glycerol