2011 ADA Posters 1261-2041.indd - Diabetes

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1735-P Cytokine Secretion from Diabetic Skeletal Muscle: Differential Regulation by LPS and Fatty Acids THEODORE P. CIARALDI, YOUNG-SUN HONG, PAMELA TAUB, SUNDER R. MUDA- LIAR, ROBERT R. HENRY, La Jolla, CA, Seoul, Republic of Korea Chronic low-grade infl ammation has been shown to contribute to the development of insulin resistance, mediated in part by increased macrophage infi ltration into adipose tissue and skeletal muscle. The possible contribution of muscle cells to the production of cytokines and chemokines was investigated using cultured human skeletal muscle cells (hSMC) from healthy subjects (H, n=4) and individuals with type 2 diabetes (T2D, n=7- 10) Myotubes were treated with lipopolysaccharide (LPS, 100 ng/mL), saturated (palmitate-Palm, 0.3 mM) and unsaturated (oleate,-Ol 0.3 mM) fatty acids or pioglitazone (Pio, 10 μM) and the media was analyzed. Under control conditions over 24 hrs, T2D hSMC released considerably more IL-8 and GROα than H muscle cells, with smaller increases in IL-6 and MCP-1. In T2D hSMC both LPS and Palm treatment signifi cantly stimulated the release of IL-6 and IL-15. Palm was more potent for these effects (ex. 557 ± 71% of IL-6 secretion from untreated cells vs 166 ± 23% with LPS, p=0.0002), also signifi cantly stimulating TNFα secretion, along with a tendency to elevate IL-8 release. Conversely, Ol treatment signifi cantly suppressed the release of IL-6, IL-8 and TNFα. Pio treatment was able to reduce the secretion of the same cytokines, though to a lesser extent than than Ol, except in the case of GROα, where it was more effective (62 ± 13% of release in paired control cells, p
Integrated Physiology/ Obesity POSTERS 1739-P Failure of Angiotensin Converting Enzyme Inhibition To Reverse Insulin Resistance in Female Obese Zucker Rats DINO PREMILOVAC, STEPHEN RATTIGAN, STEPHEN M. RICHARDS, MICHELLE A. KESKE, Hobart, Australia Impairment in insulin-mediated microvascular perfusion in muscle contri butes to the development of insulin resistance and type 2 diabetes. Angiotensin converting enzyme (ACE) inhibition has been reported to improve insulin sensitivity. Therefore, the aim of the current study was to determine whether ACE inhibition for 4 weeks improves insulin sensitivity by augmenting insulin-mediated microvascular perfusion in muscle. Female Obese Zucker (ZO) rats, at 10-12 weeks of age, were treated with quinapril (Sigma, 1mg/kg/ day provided in the drinking water) and compared to untreated ZO rats and untreated age-matched lean Zucker (LZ) rats. Following 4 weeks of treatment, overnight fasted anaesthetised rats were subjected to a hyperinsulinaemic euglycaemic clamp (20 mU/min/kg, 2hrs). Microvascular perfusion in muscle was assessed by metabolism of 1-methyl xanthine and muscle glucose uptake by 14 C-2-Deoxyglucose. After 4 weeks, untreated ZO rats had higher body weight (190±15 vs. 357±23 g, p
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2011 ADA Posters 1261-2041.indd - Diabetes

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