Pseudocholinesterase and its relationship to serum lipoproteins in diabetes mellitus

Venkatakrishnan, Annapurna (1990) Pseudocholinesterase and its relationship to serum lipoproteins in diabetes mellitus. Masters thesis, Memorial University of Newfoundland.

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Abstract

The activities of pseudocholinesterase (PChE) were compared in the serum of type I and type II diabetic patients and non-diabetic subjects. Both type I and type II diabetic patients showed increased serum PChE activity concomitant with the presence of hyperlipidemia. Pearsons correlation analysis showed a positive correlation between triglycerides (TG) and PChE in both type I (P=0.499) and type II (P=0.526) diabetic patients. -- Induction of chemical diabetes in rats with Streptozotocin (SZ) and alloxan also increased the serum PChE activity which paralleled the development of diabetes mellitus. Serum triglycerides, apo-B containing lipoproteins (total low density lipoproteins TLDL) and glycerol concentrations also increased. When the hyperglycemia produced in streptozotocin induced diabetic rats was controlled by administration of insulin, the levels of TG, glycerol and PChE activity all reverted to pre-diabetic levels. When insulin treatment was withdrawn hyperglycemia developed again and serum levels of PChE activity, TG, glycerol and TLDL also increased. The concentration of TG in the liver of SZ-diabetic rats was significantly higher compared to the normal rats. Adipose tissue and liver PChE activity were not significantly different in these SZ-diabetic rats. -- Gold thioglucose (GTG) treated mice, which are type II diabetic models, also showed a significant increase in serum PChE activity and lipids similar to the SZ induced type I diabetic models. Inhibition of PChE activity in GTG treated mice was associated with a decrease in serum glycerol, TG and TLDL levels. Liver PChE activity was markedly higher in the GTG treated mice compared to the untreated control mice. Administration of Iso-OMPA to GTG treated mice inhibited both liver and adipose tissue PChE activity. -- Heparin treatment of SZ-diabetic rats significantly reduced serum TG levels without affecting PChE activity, cholesterol, HDL-C or TLDL levels. -- Administration of Iso-OMPA, a specific PChE inhibitor, to SZ-diabetic and normal rats produced a significant reduction in serum TG, glycerol and TLDL levels. Withdrawal of iso-OMPA inhibition in the diabetic rats resulted in an increase in the lipid levels to those previously present in the diabetic state. PChE activity and TG levels were also reduced in the iso-OMPA treated diabetic and normal rat livers compared to the untreated rats. Adipose tissue PChE activity was also inhibited in the iso-OMPA treated diabetic and normal rat. -- Inhibition of PChE activity with iso-OMPA failed to produce an accumulation of choline or cholinesters in the liver, serum or to affect their excretion in the urine of normal rats. -- The results indicate that changes in PChE activity parallel changes in TG metabolism, particularly during the perturbances that accompany diabetes mellitus. Whether PChE has a role in very low density TG (VLDL-TG) metabolism remains to be determined but is of considerable interest.

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