The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase
(1999) In Diabetes Research and Clinical Practice 46(2). p.99-108- Abstract
- Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference... (More)
- Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1114139
- author
- Agardh, Carl-David LU ; Bjorgell, P and Nilsson-Ehle, Peter LU
- organization
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Tolbutamide, Lipoprotein metabolism, Lipoprotein lipase, Hormone sensitive lipase, Atherosclerosis
- in
- Diabetes Research and Clinical Practice
- volume
- 46
- issue
- 2
- pages
- 99 - 108
- publisher
- Elsevier
- external identifiers
-
- pmid:10724087
- scopus:0345363291
- ISSN
- 1872-8227
- DOI
- 10.1016/S0168-8227(99)00088-1
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Unit on Vascular Diabetic Complications (013241510), Division of Clinical Chemistry and Pharmacology (013250300)
- id
- 46902f05-3bb9-4e0d-aa27-42ba14738cbe (old id 1114139)
- date added to LUP
- 2016-04-01 12:30:07
- date last changed
- 2022-01-27 05:54:20
@article{46902f05-3bb9-4e0d-aa27-42ba14738cbe,
abstract = {{Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.}},
author = {{Agardh, Carl-David and Bjorgell, P and Nilsson-Ehle, Peter}},
issn = {{1872-8227}},
keywords = {{Tolbutamide; Lipoprotein metabolism; Lipoprotein lipase; Hormone sensitive lipase; Atherosclerosis}},
language = {{eng}},
number = {{2}},
pages = {{99--108}},
publisher = {{Elsevier}},
series = {{Diabetes Research and Clinical Practice}},
title = {{The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase}},
url = {{http://dx.doi.org/10.1016/S0168-8227(99)00088-1}},
doi = {{10.1016/S0168-8227(99)00088-1}},
volume = {{46}},
year = {{1999}},
}