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Salicylate alone, (SLY, n=9); Data are means ± SE. C) 1) Saline alone (SAL n=12), 2) Oleate alone (OLE 1.3µEq·min-1 n=10), 3) Oleate + Salicylate (OLE+SLY, oleate-1.3µEq·min-1, SLY-0.117mg·kg-1min-1, n=8), 4) Salicylate alone, (SLY, n=9); D) 1) Saline alone (SAL n=12), 2) Olive oil alone (OLO 5µl·min-1 n=7), 3) Olive oil + Salicylate (OLO+SLY, olive oil-5µl·min-1, SLY-0.117mg·kg-1min-1, n=11), 4) Salicylate alone, (SLY, n=9); Data are means ± SE. (p<0.01)
 
Ex-vivo studies in Islets: Rats were infused for 48hrs with respective treatments at the same rate as in the in-vivo study. After 48hrs islets were isolated and incubated in 2.8mmol/l (non-stimulatory), 6.5mmol/l (basal glucose level in rats), 13mmol/l and 22mmol/l (hyperglycemic clamp) of glucose (Figure 3a, 3b). GSIS in olive oil treated rats (0.996+0.132 pmol/islet/h at 22mM of glucose versus control 1.542+0.159 pmol/islet/h at 22mM) was impaired compared to saline treated rats. GSIS in oleate treated rats were also impaired when compared to control (1.033+0.097 pmol/islet/h at 22mM versus control: 1.542+0.159 pmol/islet/h at 22mM). Co-infusion of salicylate prevented the negative effects of olive oil (olive oil + salicylate: 1.754+0.367 pmol/islet/h at mM) and oleate (oleate + salicylate: 1.737+ 0.311 pmol/islet/h at 22mM) on GSIS. Salicylate alone had no effect (1.524+0.218 pmol/islet/h at 22mM).
 
Figure 3. Insulin secretory response to glucose of freshly isolated islets of 12 week old normal female Wistar rats treated for 48h with: A) 1) Saline alone (SAL n=16), 2) Oleate alone (OLE 1.3 µEq·min-1 n=14), 3) Oleate + Salicylate (OLE+SLY, oleate-1.3µ Eq·min-1, SLY-0.117 mg·kg-1min-1, n=8), 4) Salicylate alone, (SLY, n=10); B) 1) Saline alone (SAL n=16), 2) Olive oil alone (OLO 5µl·min-1 n=12), 3) Olive oil + Salicylate (OLO+SLY, olive oil-5µl·min-1, SLY-0.117mg·kg-1min-1, n=6), 4) Salicylate alone, (SLY, n=10); (p<0.01)
 
In-vitro studies: In-vitro study was carried out to investigate if 48hr infusion of oleate or co-infusion with salicylate had the same effect as in in-vivo or ex-vivo study. This would also determine whether the oleate induced impairment of GSIS is solely prevented by the addition of salicylate or whether other physiological factors also play an important role in this pathway. In-vitro, similar to in-vivo and ex-vivo, oleate impaired GSIS when compared to control (oleate: 0.212+0.026 pmol/islet/h at 22mM versus control: 0.396+0.033 pmol/islet/h at 22mM) (Figure 4). Addition of salicylate in oleate cell culture prevented the effect of oleate and restored GSIS compared to control (oleate + salicylate: 0.391+0.032 pmol/islet/h at 22mM versus control: 0.396+0.033 pmol/islet/h at 22mM). Salicylate alone had no effect (0.416+0.065 pmol/islet/h at 22mM).
 
Sensitivity Index and Disposition Index: The sensitivity index and disposition index were calculated for the two-step hyperglycemic clamp. Sensitivity index is calculated GINF divided by insulin content. 48 infusion of oleate did not have any effect on the sensitivity index when compared with saline (Figure 5a). As the two step hyperglycemic clamp demonstrated, 48hr infusion of olive oil did not impair the absolute insulin secretion as measured by the c-peptide level. This is because olive oil infusion decreased insulin sensitivity when measured by the sensitivity index (Figure 5b). The i本论文由英语论文网提供整理，提供论文代写，英语论文代写，代写论文，代写英语论文，代写留学生论文，代写英文论文，留学生论文代写相关核心关键词搜索。