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.

Q: 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.

A: Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?
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Q: Context: The purpose of this study was to examine how variation in the beta-2 adrenergic receptor gene (ADRB2), in combination with the moderating influences of race, body mass index (BMI), and anger expression style (anger-in, anger-out), affects blood pressure (BP) at rest and in response to acute laboratory stress.', 'Four hundred fifty adolescents (mean age = 18.5 +/- 2.7 years; 228 [124 males] whites and 222 [110 males] blacks completed two stressors (video game challenge, forehead cold pressor). Hemodynamic measures were taken before, during, and after each stressor. Stressors were separated by a 20-minute rest period.', 'Frequency of detrimental haplotype (Gly16/Glu27) carrier status was greater among whites than blacks (p < .05). A significant three-way interaction among haplotype, BMI, and race for resting systolic blood pressure (SBP) found the highest BP level to be among high BMI carriers, but only for whites. A separate three-way interaction was found to be significant for haplotype, anger-in and race such that high anger-in carriers showed the highest level of resting SBP (p < .05) and total peripheral resistance (TPR) (p < .05) and the greatest TPR reactivity to the cold pressor task (p < .01). Post hoc analyses revealed these interactions with anger-in were only present among blacks. No significant interactions with anger-out for either ethnic group were observed.
Answer: This study demonstrates modulating influences of BMI and anger expression styles on ADRB2 gene associations with hemodynamic function at rest and in response to laboratory stress. These findings support the hypothesis that consideration of gene-environment interactions may better characterize the role of ADRB2 variation in the development of stress-induced essential hypertension.

A: Do anger suppression and adiposity modulate association between ADRB2 haplotype and cardiovascular stress reactivity?
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Q: Context: Insulin is a major post-prandial muscle-anabolic hormone. A substantial loss of skeletal muscle mass occurs in insulin-deprived diabetes and is reversed by insulin treatment. Myostatin is a negative regulator of muscle mass upregulated in several chronic catabolic conditions. Whether myostatin expression is altered in insulin-deprived diabetes is unknown. In spite of opposite effects on muscle mass the potential role of basal circulating insulin in the regulation of myostatin expression is also undetermined.', 'We measured (Northern Blot) myostatin transcript levels in muscle groups with different fiber composition in streptozotocin-diabetic male rats receiving one of the following treatments for eight weeks: (1) control (C); (2) diabetes without treatment (DM); (3) diabetes with once-daily slow-acting insulin treatment (INS).', 'INS normalized plasma insulin and prevented weight reduction observed in DM. In fast-twitch gastrocnemius muscle myostatin transcript levels were unchanged (P>0.4) in both DM and INS compared to C. Myostatin transcripts were not measurable in any group in slow-twitch soleus muscle.
Answer: Muscle-specific myostatin expression is not increased under catabolic conditions in insulin-deprived diabetes. Insulin treatment also does not change myostatin transcript levels. The data provide the first assessment of potential interplay between insulin and myostatin and they do not support a major role of circulating insulin in the in vivo regulation of myostatin gene expression. A role of myostatin in muscle catabolism in chronic insulin-deprived diabetes is also not indicated by the current results.

A:
Is myostatin expression altered by insulin deficiency and replacement in streptozotocin-diabetic rat skeletal muscles?
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