Abstract
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)
Highlights
Patients with diabetes commonly manifest hypertriglyceridemia along with decreased adipose tissue lipopre tein lipase (WL) activity, and improved diabetes control tends to reverse these abnormalities
Treatment with either insulin or glyburide led to similar improvements in glycemic control, as shown by the significant fall in glycohemoglobin and fasting glucose (Table 1).In addition, there was a significant decrease in plasma triglycerides and cholesterol, without change in high density lipoprotein (HDL) cholesterol
HR lipoprotein lipase (LPL) activity was 0.97f0.52 nEq FFA released/min per lo6 cells, and increased to 1.64k 0.69; and EXT LPL activitywas 0.28k0.17 and increased to 1.08f0.33 nEq FFA released/min per 106 cells following treatment. The levels of both HR and EXT LPL immunoreactive mass increased from 2.39 k 0.62 to 5.15 f 1.76 ng/106 cells, and from 6.24 f 1.06 to 17.0 rt 4.89 ng/106 cells, respectively, suggesting that the increase in LPL activity was due to an increase in LPL protein (Fig. 1, panel B)
Summary
Patients with diabetes commonly manifest hypertriglyceridemia along with decreased adipose tissue lipopre tein lipase (WL) activity, and improved diabetes control tends to reverse these abnormalities. Improved glycemic control resulted in an increase in LPL activity which correlated with each patient's basal high density lipoprotein. Numerous studies have described decreases in LPL catalytic activity in the adipose tissue [2,3,4] or the post-heparin plasma [5, 6] of both insulindependent (IDD) and non-insulindependent diabetics (NIDD) who are under poor glycemic control. Subsequent treatment of these patients has been shown to increase the level of lipoprotein lipase, coincident with a fall m plasma triglycerides. To study the defect in LPL regulation in diabetes, we examined the mechanism of regulation of adipose tissue LPL after improvement of glycemic control either with insulin or sulfonylurea drug treatment
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