β-Cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome.
Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 μg/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into β-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden Division of Drug Research, Experimental Renal Medicine, Department of Medical and Health Sciences Center of Medical Image Science and Visualization, Linköping University, SE-581 83 Linköping, Sweden Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama 36688, USA.
Liselotte
L
Fransson
Stephanie
S
Franzén
Victoria
V
Rosengren
Petra
P
Wolbert
Åke
Å
Sjöholm
Henrik
H
Ortsäter
D050154:Adiposity; D000284:Administration, Oral; D052636:Allostasis; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000209:etiology; D002149:Energy Intake; D005938:Glucocorticoids / Q000008:administration & dosage; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000503:physiopathology*; D015430:Weight Gain
D005938:Glucocorticoids
diabetes; glucocorticoid; insulin secretion; islet cells; obesity