Author/Editor     Mulder, Hindrik; Soerhede-Winzell, Maria; Contreras, Juan Antonio; Fex, Malin; Stroem, Kristoffer; Ploug, Thorkil; Galbo, Henrik; Arner, Peter; Lundberg, Cecilia; Sundler, Frank; Ahren, Bo; Holm, Cecilia
Title     Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact
Type     članek
Source     J Biol Chem
Vol. and No.     Letnik 278, št. 38
Publication year     2003
Volume     str. 36380-8
Language     eng
Abstract     Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption of the HSL gene for glucose homeostasis were examined. HSL null mice were slightly hyperglycemic in the fasted, but not fed state, which was accompanied by moderate hyperinsulinemia. During glucose challenges, however, disposal of the sugar was not affected in HSL null mice, presumably because of release of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance. Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia.
Descriptors     ADIPOCYTES
ADIPOSE TISSUE
ARGININE
BLOTTING, WESTERN
BODY WEIGHT
CHOLESTEROL ESTERASE
DNA, COMPLEMENTARY
DOSE-RESPONSE RELATIONSHIP, DRUG
EXONS
GLUCOSE
GLUCOSE TOLERANCE TEST
HYPERGLYCEMIA
IMMUNOHISTOCHEMISTRY
INSULIN
ISLETS OF LANGERHANS
ISOPROTERENOL
LIVER
MICE
MICE, TRANSGENIC
MICROSCOPY, FLUORESCENCE
MUSCLE, SKELETAL
TIME FACTORS