Patients with diabetes commonly manifest
hypertriglyceridemia along with decreased adipose tissue
lipoprotein lipase (LPL) activity, and improved diabetes control tends to reverse these abnormalities. To better understand the mechanism of regulation of LPL in diabetes, 11 diabetic patients (3 type I, 8 type II) were brought under improved
glycemic control, and adipose tissue LPL gene expression was assessed by performing paired fat biopsies. Six of the 11 patients attained improved control with
insulin, with a decrease in
glycohemoglobin (glyc Hgb) from 13.8 +/- 0.9 to 10.4 +/- 0.6%; 5 patients attained improved control with
glyburide (glyc Hgb fell from 14.2 +/- 2.4 to 8.8 +/- 0.6%), and together they demonstrated a lowering of serum
triglycerides and total
cholesterol. No changes were observed in
HDL cholesterol. Improved diabetes control resulted in a significant increase in LPL activity in both the
heparin-releasable (HR) and extractable (EXT) fractions of adipose tissue, as well as in LPL immunoreactive mass. The change in LPL activity with improved control was variable, and showed a positive correlation with the HDL levels prior to treatment (r = 0.74, P less than 0.02). When adipose tissue was pulse-labeled with [35S]
methionine, there was an increase in
isotope incorporation into LPL
after treatment, indicating an increase in LPL synthetic rate. However, improved diabetes control resulted in no significant change in LPL
mRNA levels. Thus, improved
glycemic control resulted in an increase in LPL activity which correlated with each patient's basal
high density lipoprotein. This increase in LPL activity was accompanied by an increase in LPL immunoreactive mass, and an increase in LPL synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)