title: Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion.
abstract: Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca(2+) signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Vishal A
authors.initials: VA
authors.lastname: Salunkhe
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Inês G
authors.initials: IG
authors.lastname: Mollet
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Jones K
authors.initials: JK
authors.lastname: Ofori
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Malm
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Jonathan L S
authors.initials: JL
authors.lastname: Esguerra
authors.affiliation: Inst. Neuroscience and Physiology, Dept of Physiology, University of Gothenburg, Medicinaregatan 11-13, Box 432, 405 30 Gothenburg, Sweden.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Reinbothe
authors.affiliation: Unit of Glucose Transport and Protein Trafficking, Dept of Experimental Medical Sciences, Lund University Diabetes Centre, Lund University BMC-C11, Sölvegatan 21, 222 84 Lund, Sweden.
authors.forename: Karin G
authors.initials: KG
authors.lastname: Stenkula
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wendt
authors.affiliation: Unit of Islet Cell Exocytosis, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 91-11, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. Electronic address: lena.eliasson@med.lu.se.
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
authors.affiliation: Unit of Diabetes and Endocrinology, Dept Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University CRC 60-13, SUS Malmö, Jan Waldenströms gata 35, 205 02 Malmö, Sweden. Electronic address: jenny.vikman@med.lu.se.
authors.forename: Jenny
authors.initials: J
authors.lastname: Vikman
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D059305:Diet, High-Fat; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D000068718:Rosuvastatin Calcium; D005947:Glucose; D002118:Calcium
keywords: Adipose tissue; Beta cell; Ca(2+) measurements; Glucose homeostasis; Glucose uptake; Insulin secretion; Islet; Muscle; OGTT; Statin; Transmission electron microscopy