Title
Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice
Author
Voshol, P.J.
Haemmerle, G.
Ouwens, D.M.
Zimmermann, R.
Zechner, R.
Teusink, B.
Maassen, J.A.
Havekes, L.M.
Romijn, J.A.
Publication year
2003
Abstract
Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine whether a hepatic TG content lower than normal, as observed in HSL-knockout mice, leads to increased hepatic insulin sensitivity. Therefore, hyperinsulinemic clamp experiments in combination with D-3H. glucose were used. Furthermore, hepatic insulin receptor and phosphorylated protein kinase B (PKB-P)/akt were analyzed by Western blotting. No significant differences where observed in insulin-mediated whole-body glucose uptake between HSL-knockout and control mice. Interestingly, hepatic insulin sensitivity of HSL-knockout mice was increased, because insulin caused a greater reduction in endogenous glucose production (∼71% compared with ∼31% in control mice; P < 0.05), despite decreased plasma adiponectin levels. PKB/akt phosphorylation and phosphatidylinositol-3-kinase activity was significantly higher in livers of HSL-knockout mice after insulin stimulation. In HSL-knockout mice, reduced hepatic TG stores result in an increased suppressive effect of insulin on hepatic glucose production, in line with an increased hepatic PKB-P/akt and phosphatidylinositol-3 kinase activity. Thus, hepatic insulin sensitivity is indeed increased after reducing hepatic TG stores below normal.
Subject
Health
Glucose
Hormone sensitive lipase
Insulin receptor
Protein kinase B
Triacylglycerol
Triacylglycerol lipase
Unclassified drug
Animal tissue
Controlled study
Enzyme activity
Enzyme deficiency
Enzyme mechanism
Enzyme phosphorylation
Fatty acid blood level
Gluconeogenesis
Glucose transport
Hormone sensitivity
Hyperinsulinemia
Insulin sensitivity
Knockout mouse
Lipid liver level
Lipolysis
Mouse
Nonhuman
Western blotting
Adiponectin
Animals
Blood Glucose
Cholesterol
Cholesterol Esterase
Fasting
Fatty Acids, Nonesterified
Glucose
Insulin
Intercellular Signaling Peptides and Proteins
Liver
Male
Mice
Mice, Knockout
Muscle, Skeletal
Proteins
Receptor, Insulin
Triglycerides
To reference this document use:
http://resolver.tudelft.nl/uuid:01ad5532-d637-44f7-ac5d-b99faa97cda4
DOI
https://doi.org/10.1210/en.2002-0036
TNO identifier
237212
ISSN
0013-7227
Source
Endocrinology, 144 (8), 3456-3462
Document type
article