Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.

Hindrik Mulder; Maria Sörhede-Winzell; Juan Antonio Contreras; Malin Fex; Kristoffer Ström; Thorkil Ploug; Henrik Galbo; Peter Arner; Cecilia Lundberg; Frank Sundler; Bo Ahrén; Cecilia Holm

doi:10.1074/jbc.M213032200

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.

Hindrik Mulder, Maria Sörhede-Winzell, Juan Antonio Contreras, Malin Fex, Kristoffer Ström, Thorkil Ploug, Henrik Galbo, Peter Arner, Cecilia Lundberg, Frank Sundler, Bo Ahrén, Cecilia Holm

Biomedicinsk Institut

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

107 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Sep-19

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	278
Udgave nummer	38
Sider (fra-til)	36380-8
Antal sider	8
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M213032200
Status	Udgivet - 2003

Bibliografisk note

Keywords: Adipocytes; Adipose Tissue; Animals; Arginine; Blotting, Western; Body Weight; DNA, Complementary; Dose-Response Relationship, Drug; Exons; Female; Glucose; Glucose Tolerance Test; Hyperglycemia; Immunohistochemistry; Insulin; Islets of Langerhans; Isoproterenol; Lipid Metabolism; Liver; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence; Muscle, Skeletal; Sterol Esterase; Time Factors

Adgang til dokumentet

10.1074/jbc.M213032200

Citationsformater

Mulder, H., Sörhede-Winzell, M., Contreras, J. A., Fex, M., Ström, K., Ploug, T., Galbo, H., Arner, P., Lundberg, C., Sundler, F., Ahrén, B., & Holm, C. (2003). Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact. Journal of Biological Chemistry, 278(38), 36380-8. https://doi.org/10.1074/jbc.M213032200

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title = "Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.",

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.",

author = "Hindrik Mulder and Maria S{\"o}rhede-Winzell and Contreras, {Juan Antonio} and Malin Fex and Kristoffer Str{\"o}m and Thorkil Ploug and Henrik Galbo and Peter Arner and Cecilia Lundberg and Frank Sundler and Bo Ahr{\'e}n and Cecilia Holm",

note = "Keywords: Adipocytes; Adipose Tissue; Animals; Arginine; Blotting, Western; Body Weight; DNA, Complementary; Dose-Response Relationship, Drug; Exons; Female; Glucose; Glucose Tolerance Test; Hyperglycemia; Immunohistochemistry; Insulin; Islets of Langerhans; Isoproterenol; Lipid Metabolism; Liver; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence; Muscle, Skeletal; Sterol Esterase; Time Factors",

year = "2003",

doi = "10.1074/jbc.M213032200",

language = "English",

volume = "278",

pages = "36380--8",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

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TY - JOUR

T1 - Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.

AU - Mulder, Hindrik

AU - Sörhede-Winzell, Maria

AU - Contreras, Juan Antonio

AU - Fex, Malin

AU - Ström, Kristoffer

AU - Ploug, Thorkil

AU - Galbo, Henrik

AU - Arner, Peter

AU - Lundberg, Cecilia

AU - Sundler, Frank

AU - Ahrén, Bo

AU - Holm, Cecilia

N1 - Keywords: Adipocytes; Adipose Tissue; Animals; Arginine; Blotting, Western; Body Weight; DNA, Complementary; Dose-Response Relationship, Drug; Exons; Female; Glucose; Glucose Tolerance Test; Hyperglycemia; Immunohistochemistry; Insulin; Islets of Langerhans; Isoproterenol; Lipid Metabolism; Liver; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence; Muscle, Skeletal; Sterol Esterase; Time Factors

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M213032200

DO - 10.1074/jbc.M213032200

M3 - Journal article

C2 - 12835327

SN - 0021-9258

VL - 278

SP - 36380

EP - 36388

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 38

ER -