Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.', 'The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.', 'Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).
Answer: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.
Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?

Context: Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated as a key mediator of reperfusion injury. Activation of NF-kappaB is dependent upon the phosphorylation of its inhibitor, IkappaB, by the specific inhibitory kappaB kinase (IKK) subunit, IKKbeta. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKbeta. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-kappaB, we approached the relationship between NGAL and IKKbeta.', 'Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKbeta in renal tissues.', 'Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 +/- 12.98 vs. 205.89 +/- 19.16 mircomol/l, p < 0.01; tubulointerstitial injury scores, 1.3 +/- 0.48 vs. 3.8 +/- 0.79, p < 0.01). In addition, expressions of IKKbeta (0.95 +/- 0.21 vs. 1.74 +/- 0.17, p < 0.05) and NGAL (1.71 +/- 0.032 vs. 2.66 +/- 0.078, p < 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKbeta and NGAL were in positive correlation (R = 0.965 > R(0.01)(30) = 0.448, p < 0.01).
Answer: The evidence suggests that IKKbeta may play a role in renal I/R injury and give rise to the generation of NGAL. It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKbeta may offer a clinically accessible target for preventing renal injury following I/R.
Does ischemic preconditioning attenuate renal ischemia-reperfusion injury by inhibiting activation of IKKbeta and inflammatory response?

Context: The objective of this study was to determine the effects of different doses of gamma-emitting radioactive stents on intimal hyperplasia in a porcine coronary stent model at 28 days.', 'Sixty-four bare stents and those coated with palladium-103 [activities of 0 (control), 0.5, 1.0, 2.0, and 4.0 mCi] were implanted in the coronary arteries of 32 pigs. Stented segments were evaluated by histomorphometry at 28 days.', 'There was significantly more intima in the 0.5- and 1-mCi stents than in controls (4.27+/-0.52 and 4.71+/-1.13 vs. 1.71+/-0.61 mm(2); P<.0001). Neointimal formation in 2-mCi stents was similar to that in controls, while that in 4-mCi stents was reduced compared to that in controls (2.34+/-1.61 and 0.82+/-0.25 vs. 1.71+/-0.61 mm(2); P=NS and P<.05, respectively). Stent margin neointimal response was representative of that within the stent body, with nonsignficant modest increases in intimal area at adjacent nonstented segments in radioactive stent groups. There was a dose-dependent increase in inflammation scores. Radioactive stents had lower intimal smooth muscle and higher fibrin scores. There was an increase in adventitial fibrosis in 1- and 2-mCi stents versus controls (1.26+/-0.99, and 2.25+/-1.27 vs. 0.21+/-0.31; P<.001).
Answer: Dose-response inhibition of in-stent hyperplasia with minimal "edge effects" occurs with low-energy gamma-emitting stents. An increased inflammatory response at higher doses in palladium-103 stents indicates that later follow-up studies are necessary.

Do low-energy gamma-emitting stents inhibit intimal hyperplasia with minimal `` edge effects '' in a pig coronary artery model?