RESUMO
Background: Several amino acids and their derivatives have been implicated in insulin resistance (IR) and Type 2 Diabetes Mellitus (T2DM). This research sought to establish a relationship between the dietary levels of branched-chain amino acids (BCAA) and the risk of T2DM. Methods: This case-control study was carried out on 4200 participants consisting of 589 people with T2DM and 3611 non-diabetic aged 35 to 70 years residents in Sabzevar, Iran. Data on the economic-social, employment status, medical history, lifestyle, and sleep habits were collected via interview. The food frequency questionnaire (FFQ) was used to check the nutritional status. Participants' dietary BCAA consumption was estimated using Nutritionist IV software. Results: A significant negative association between the incidence of T2DM and the dietary levels of BCAAs after adjustment for age and sex (OR = 0.972, CI 95%:0.648-0.996, P = 0.022). The negative association remained significant after additional adjustments for body mass index (BMI) and physical activity (OR = 0.967, CI 95%: 0.943-0.992, P = 0.010). Interestingly, a positive association was found between T2DM and total BCAAs (OR = 1.067, CI 95%: 1.017-1.119, P = 0.008), Isoleucine (OR = 1.248, CI 95%: 1.043-1.494, P = 0.016), Leucine (OR = 1.165, CI 95%: 1.046-1.299, P = 0.006) and Valine (OR = 1.274, CI 95%: 1.088-1.492, P = 0.003) after further adjustment for calorie intake. Conclusions: Our results demonstrate branched-chain amino acids (BCAAs) including isoleucine, leucine, and valine are negatively associated with the incidence of type 2 diabetes (T2DM) after adjusting for age and sex, BMI, and physical activity. However, adjusting for calorie intake reversed the association between T2DM and BCAAs. These findings suggest that the association between BCAAs and T2DM may be influenced by calorie intake. Future longitudinal studies are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01247-9.
RESUMO
BACKGROUND: In this study, we evaluated the effects of atorvastatin, a lipid-lowering medication on morphine-induced tolerance and dependence in mice. METHODS: Tolerance was induced by subcutaneous administration of morphine (20mg/kg) to animals, twice a day for 9days. Atorvastatin was given at the doses of 5, 10 and 20mg/kg, 30min before each morphine administration, once daily for 9days. Hot plate test was employed to assess antinociceptive effect of morphine on days 1, 3, 5, 7 and 9. Dependence was evaluated by naloxone-precipitated withdrawal syndrome. We attempted to verify withdrawal regulation of induced nitric oxide synthase (iNOS), astroglia marker, glial fibrillary acidic protein (GFAP), ionized calcium-binding protein (Iba1), a microglia activation marker, a pro-inflammatory mediator, tumor necrosis alpha (TNF-α) and immune receptor, toll like receptor 4 (TLR-4) genes by real-time polymerase chain reaction (RT-PCR). Lipid peroxidation was estimated by assessing malondialdehyde (MDA) content in the spinal cord of animals. RESULTS: Tolerance to antinociceptive effects of morphine was observed on days 7 and 9. Decrease in morphine-induced antinociception was reversed by concomitant intraperitoneal administration of atorvastatin (10 and 20mg/kg). Atorvastatin (10 and 20mg/kg) mitigated naloxone-induced withdrawal parameters. Brain expression levels of TNF-α, GFAP, Iba1 and iNOS increased in morphine withdrawn animals which were attenuated by nine days treatment with atorvastatin. Increased MDA was also normalized in withdrawn animals received atorvastatin. CONCLUSION: Atorvastatin exhibits meaningful protective effects against both tolerance to antinociceptive effects of morphine and withdrawal-induced behavioral profile. Neuroprotective effects of atorvastatin is further supported via inhibition of glia activity and antioxidant effects.