title: Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic beta-cell function and mass through IRS2 in diabetic rats.
abstract: In this study, we investigated the effects of a high-fat diet and exercise on pancreatic beta-cell function and mass and its molecular mechanism in 90% pancreatectomized male rats. The pancreatectomized diabetic rats were given control diets (20% energy) or a high-fat (HF) diet (45% energy) for 12 wk. Half of each group was given regular exercise on an uphill treadmill at 20 m/min for 30 min 5 days/wk. HF diet lowered first-phase insulin secretion with glucose loading, whereas exercise training reversed this decrease. However, second-phase insulin secretion did not differ among the groups. Exercise increased pancreatic beta-cell mass. This resulted from stimulated beta-cell proliferation and reduced apoptosis, which is associated with potentiated insulin or IGF-I signaling through insulin receptor substrate-2 (IRS2) induction. Although the HF diet resulted in decreased proliferation and accelerated apoptosis by weakened insulin and IGF-I signaling from reduction of IRS2 protein, beta-cell mass was maintained in HF rats just as much as in control rats via increased individual beta-cell size and neogenesis from precursor cells. Consistent with the results of beta-cell proliferation, pancreas duodenal homeobox-1 expression increased in the islets of rats in the exercise groups, and it was reduced the most in rats fed the HF diet. In conclusion, exercise combined with a moderate fat diet is a good way to maximize beta-cell function and mass through IRS2 induction to alleviate the diabetic condition. This study suggests that dietary fat contents and exercise modulate beta-cell function and mass to overcome insulin resistance in two different pathways.
authors.affiliation: Dept. of Food and Nutrition, College of Natural Science, Institutes of Basic Sciences, Hoseo Univ., 165 Sechul-Ri Baebang-Myun Asan-Si, Chungnam-Do, 336-795, Korea. smpark@hoseo.edu
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hong
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: So Ra
authors.initials: SR
authors.lastname: Sung
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism*; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004041:Dietary Fats / Q000378:metabolism*; D005081:Exercise Therapy; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D010180:Pancreatectomy; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D018398:Homeodomain Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein