Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function.
Exercise improves glucose tolerance in obese rodent models and humans; however, effects with respect to mechanisms of beta-cell compensation remain unexplained. We examined exercise's effects during the progression of hyperglycemia in male Zucker diabetic fatty (ZDF) rats until 19 wk of age. At 6 wk old, rats were assigned to 1) basal--euthanized for baseline values; 2) exercise--swam individually for 1 h/day, 5 days/wk; and 3) controls (n = 8-10/group). Exercise (13 wk) resulted in maintenance of fasted hyperinsulinemia and prevented increases in fed and fasted glucose (P < 0.05) compared with sham-exercised and sedentary controls (P < 0.05). Beta-cell function calculations indicate prolonged beta-cell adaptation in exercised animals alone. During an intraperitoneal glucose tolerance test (IPGTT), exercised rats had lower 2-h glucose (P < 0.05) vs. controls. Area-under-the-curve analyses from baseline for IPGTT glucose and insulin indicate improved glucose tolerance with exercise was associated with increased insulin production and/or secretion. Beta-cell mass increased in exercised vs. basal animals; however, mass expansion was absent at 19 wk in controls (P < 0.05). Hypertrophy and replication contributed to expansion of beta-cell mass; exercised animals had increased beta-cell size and bromodeoxyuridine incorporation rates vs. controls (P < 0.05). The relative area of GLUT2 and protein kinase B was significantly elevated in exercised vs. sedentary controls (P < 0.05). Last, we show formation of ubiquitinated protein aggregates, a response to cellular/oxidative stress, occurred in nonexercised 19 wk-old ZDF rats but not in lean, 6 wk-old basal, or exercised rats. In conclusion, improved beta-cell compensation through increased beta-cell function and mass occurs in exercised but not sedentary ZDF rats and may be in part responsible for improved glucoregulation.
Király
Michael A
MA
Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
Bates
Holly E
HE
Kaniuk
Natalia A
NA
Yue
Jessica T Y
JT
Brumell
John H
JH
Matthews
Stephen G
SG
Riddell
Michael C
MC
Vranic
Mladen
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002096:C-Peptide / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D004435:Eating / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006943:Hyperglycemia / Q000517:prevention & control*; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D019518:Postprandial Period; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013550:Swimming / Q000502:physiology*
D001786:Blood Glucose; D002096:C-Peptide; D051273:Glucose Transporter Type 2; D007328:Insulin; C495683:Slc2a2 protein, rat; D051058:Oncogene Protein v-akt; D051057:Proto-Oncogene Proteins c-akt