The prevalence of Type 2 Diabetes Mellitus (T2DM), a serious and costly disease, has increased dramatically in the past 2 decades. Current therapies for diabetes are expensive and are unable to prevent the long-term complications of the disease. New strategies to prevent or delay the onset of type 2 diabetes would prevent or delay the onset of diabetic complications, and therefore decrease patient suffering and save the health care system billions of dollars. We have recently developed a new rat model of type 2 diabetes that exhibits both adult-onset obesity induced insulin resistance and an impairment of pancreatic Beta-cell function. This model is more relevant to type-2 diabetes in humans and therefore an appropriate animal model for testing new approaches for diabetes prevention. We propose to determine the efficacy of several widely used nutritional supplements known to activate PPARs and/or target lipid dysregulation, inflammation, and oxidative stress to prevent or delay the onset of T2DM in this rat model. We will pursue the following specific aims:
Specific Aim 1 : We hypothesize that supplementation with omega 3 fatty acid eicosapentaenoic acid (EPA) will activate PPARalpha, gamma and delta and prevent or delay the onset of T2DM. We will also determine whether purified EPA will attenuate the development of diabetes more effectively than fish oil supplements.
Specific Aim 2 : We hypothesize that supplementation with a-lipoic acid will reduce oxidative stress, thereby preventing or delaying onset of T2DM. We will also investigate whether a-lipoic acid in combination with the marine oil PPAR activators (EPA & DMA) will be more effective than a-lipoic acid alone in preventing diabetes. Further studies to investigate the mechanism(s) of action of the supplements or the supplement combinations that are effective in preventing/delaying diabetes onset of diabetes in this model are proposed. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT002993-01
Application #
6963548
Study Section
Special Emphasis Panel (ZAT1-DB (18))
Program Officer
Klein, Marguerite
Project Start
2005-09-01
Project End
2008-06-30
Budget Start
2005-09-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$176,500
Indirect Cost
Name
University of California Davis
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Fields, Aaron J; Berg-Johansen, Britta; Metz, Lionel N et al. (2015) Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes. J Orthop Res 33:738-46
Agrawal, Rahul; Zhuang, Yumei; Cummings, Bethany P et al. (2014) Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes. Biochim Biophys Acta 1842:1313-23
Rountree, A M; Reed, B J; Cummings, B P et al. (2013) Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes. Diabetologia 56:803-13
Cummings, Bethany P; Graham, James L; Stanhope, Kimber L et al. (2013) Maternal ileal interposition surgery confers metabolic improvements to offspring independent of effects on maternal body weight in UCD-T2DM rats. Obes Surg 23:2042-9
Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L et al. (2013) Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech 6:443-56
Cummings, Bethany P; Bremer, Andrew A; Kieffer, Timothy J et al. (2013) Investigation of the mechanisms contributing to the compensatory increase in insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques. J Endocrinol 216:207-15
Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L et al. (2012) Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats. Endocrinology 153:3620-32
Cox, C L; Stanhope, K L; Schwarz, J M et al. (2012) Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women. Eur J Clin Nutr 66:201-8
Lee, Jennifer; Cummings, Bethany P; Martin, Elizabeth et al. (2012) Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol 302:R657-66
Yang, Ri-Yao; Yu, Lan; Graham, James L et al. (2011) Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice. Proc Natl Acad Sci U S A 108:18696-701

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