title: The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats.
abstract: Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C:F) in streptozotocin (STZ)-treated diabetic rats. STZ (65 mg/kg) was intraperitoneally administered to male Sprague-Dawley rats (n= 36) to induce diabetes, with healthy, nondiabetic, sedentary rats (n= 10) as controls. The STZ-treated rats were then divided into sedentary (SED) or exercising (EX; 24-h access to running wheels) groups and then further subdivided into prazosin (Praz) or water (H2O) treatment groups: nondiabetic-SED-H2O, STZ-SED-H2O, STZ-EX-H2O, STZ-SED-Praz, and STZ-EX-Praz. After 3 wk, untreated diabetes significantly reduced the C:F in tibialis anterior (TA) and soleus muscles in the STZ-SED-H2O animals (bothP< 0.05). Voluntary exercise and prazosin treatment independently resulted in a normalization of C:F within the TA (1.86 ± 0.12 and 2.04 ± 0.03 vs 1.71 ± 0.09,P< 0.05) and the soleus (2.36 ± 0.07 and 2.68 ± 0.14 vs 2.13 ± 0.12,P< 0.05). The combined STZ-EX-Praz group resulted in the highest C:F within the TA (2.26 ± 0.07,P< 0.05). Voluntary exercise volume was negatively correlated with fed blood glucose levels (r2= -0.7015,P< 0.01) and, when combined with prazosin, caused further enhanced nonfasted glucose (P< 0.01). Exercise and prazosin reduced circulating nonesterified fatty acids more than either stimulus alone (P< 0.05). These results suggest that the distinct stimulation of angiogenesis, with both regular exercise and prazosin treatment, causes a cooperative improvement in the microvascular complications associated with T1D.NEW & NOTEWORTHYIt is currently well established that poorly controlled diabetes reduces both skeletal muscle mass and muscle capillarization. These muscle-specific features of diabetes may, in turn, compromise insulin sensitivity and glucose control. Using a model of streptozotocin-induced diabetes, we show the vascular complications linked with disease and how chronic exposure to exercise and prazosin (an α1-adrenergic antagonist) can reduce these complications and improve glycemic control.
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Dunford
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Erwan
authors.initials: E
authors.lastname: Leclair
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Aiken
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Mandel
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Tara L
authors.identifier: http://orcid.org/0000-0001-8559-9574
authors.initials: TL
authors.lastname: Haas
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Birot
authors.affiliation: School of Kinesiology and Health Science, Faculty of Health, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, York University, Toronto, Ontario, Canada mriddell@yorku.ca.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Riddell
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology* / Q000628:therapy*; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D005081:Exercise Therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000073436:Microvascular Rarefaction / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology* / Q000628:therapy*; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016896:Treatment Outcome; D014836:Volition
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013311:Streptozocin; D011224:Prazosin
keywords: capillaries; diabetes; exercise; muscle; prazosin