title: Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat.
abstract: Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.
authors: Molecular Nutrition Unit and The Montreal Diabetes Research Center, Research Center of the University of Montreal Hospital Center,University of Montreal, Quebec, Canada.
authors: Viviane
authors: V
authors: Delghingaro-Augusto
authors: Simon
authors: S
authors: Décary
authors: Marie-Line
authors: ML
authors: Peyot
authors: Martin G
authors: MG
authors: Latour
authors: Julien
authors: J
authors: Lamontagne
authors: Nicolas
authors: N
authors: Paradis-Isler
authors: Marianne
authors: M
authors: Lacharité-Lemieux
authors: Huguette
authors: H
authors: Akakpo
authors: Olivier
authors: O
authors: Birot
authors: Christopher J
authors: CJ
authors: Nolan
authors: Marc
authors: M
authors: Prentki
authors: Raynald
authors: R
authors: Bergeron
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004435:Eating / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D005227:Fatty Acids; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D000324:Adrenocorticotropic Hormone