G. Holdsworth

Insulin-independent diabetes: A defect in the activity of lipoprotein lipase in adipose tissue

SummaryThe activity of lipoprotein lipase (E.C.3.1.1.3.) has been measured in adipose tissue from insulin-independent diabetics with hypertriglyceridaemia, non-diabetics with hypertriglyceridaemia and control patients, all of whom were obese. Although all groups showed an increase of plasma insulin after oral glucose, both the diabetic and nondiabetic hypertriglyceridaemics had impaired activities of lipoprotein lipase in adipose tissue compared to the obese normals (p<0.02, p<0.03, respectively). A course of insulin therapy (20 u.o.d.) for one week increased the activity of lipoprotein lipase extracted from adipose tissue, lowered plasma triglycerides and improved triglyceride clearance from plasma in a group of diabetics with hypertriglyceridaemia (mean plasma triglyceride 8.7 mmol/l). Our results suggest that a feature in the development of insulin resistance in adult diabetics may be a failure of maintenance of key intracellular enzyme activities involved in lipid metabolism.

CLOFIBRATE INCREASES LIPOPROTEIN-LIPASE ACTIVITY IN ADIPOSE TISSUE OF HYPERTRIGLYCERIDÆMIC PATIENTS

Clearance of plasma-triglycerides and activity of lipoprotein lipase in adipose tissue were studied in six hypertriglyceridaemic patients before and after a week of clofibrate therapy (2 g/day). Plasma-triglycerides decreased significantly from 6.85 +/- 1.1 to 2.66 +/- 0.29 mmol/l and triglyceride clearance increased significantly from 1.3 +/- 0.2 to 2.4 +/- 0.4%/min. There were concomitant significant increases in heparin-releasable lipoprotein lipase (95 +/- 16 to 181 +/- 34 nmol free fatty acids/10(6) cells/h) and in extractable lipase (88 +/- 14 to 179 +/- 28 nmol free fatty acids/10(6) cells/h). It is concluded that an important effect of clofibrate may be to increase the levels of adipose-tissue lipoprotein lipase and thereby improve the clearance of plasma-triglycerides.

An abnormal triglyceride-rich lipoprotein carrying excess apolipoprotein C-II

The polypeptide composition of a variant lipoprotein (d less than 1.006) carrying a relative excess of apolipoprotein C-II has been characterised by polyacrylamide gel electrophoresis and isoelectric focussing. The apo-C peptides of the variant lipoprotein contained 45.2 +/- 1.3 (n = 9) % of apo C-II compared with 21.5 +/- 5.4 (n = 30) % for hypertriglyceridaemic controls. The variant lipoprotein activated purified bovine milk lipoprotein lipase normally, but was an inefficient substrate for this enzyme as assessed by direct release of fatty acids from the lipoprotein or by a substrate competition assay. Electron microscopy revealed the variant lipoprotein as non-spherical flattened particles compared with the more spherical appearance of control triglyceride-rich lipoproteins. We suggest that the relative proportion of apo C peptides associated with the lipoprotein particle may be critical for optimal enzyme-substrate interaction.