All-trans retinoic acid impairs glucose-stimulated insulin secretion by activating the RXR/SREBP-1c/UCP2 pathway.

Diabetes is often associated with vitamin A disorders. All-trans retinoic acid (ATRA) is the main active constituent of vitamin A. We aimed to investigate whether ATRA influences diabetic progression and its mechanisms using both Goto-Kazizazi (GK) rats and INS-1 cells. Rat experiments demonstrated that ATRA treatment worsened diabetes symptoms, as evidenced by an increase in fasting blood glucose (FBG) levels and impairment of glucose homeostasis. Importantly, ATRA impaired glucose-stimulated insulin secretion (GSIS) and increased the expression of sterol regulatory element-binding protein 1c (SREBP-1c) and uncoupling protein 2 (UCP2) in the rat pancreas. Data from INS-1 cells also showed that ATRA upregulated SREBP-1c and UCP2 expression and impaired GSIS at 23 mM glucose. Srebp-1c or Ucp2 silencing attenuated GSIS impairment by reversing the ATRA-induced increase in UCP2 expression and decrease in ATP content. ATRA and the retinoid X receptor (RXR) agonists 9-cis RA and LG100268 induced the gene expression of Srebp-1c, which was almost completely abolished by the RXR antagonist HX531. RXRα-LBD luciferase reporter plasmid experiments also demonstrated that ATRA concentration-dependently activated RXRα, the EC50 of which was 1.37 µM, which was lower than the ATRA concentration in the pancreas of GK rats treated with a high dose of ATRA (approximately 3 µM), inferring that ATRA can upregulate Srebp-1c expression in the pancreas by activating RXR. In conclusion, ATRA impaired GSIS partly by activating the RXR/SREBP-1c/UCP2 pathway, thus worsening diabetic symptoms. The results highlight the roles of ATRA in diabetic progression and establish new strategies for diabetes treatment.

[Acupuncture and moxibustion for vascular dementia and its effect on serum VEGF and AChE].

OBJECTIVE: To observe the efficacy of Huayu Tongluo moxibustion combined with acupuncture at Jing-well points on the differentiated meridians and routine acupuncture for vascular dementia (VD) and its effect on serum levels of vascular endothelial growth factor (VEGF) and acetylcholinesterase (AChE). METHODS: A total of 60 patients with VD were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, Huayu Tongluo moxibustion combined with acupuncture at Jing-well points on the differentiated meridians and routine acupuncture were adopted, Huayu Tongluo moxibustion was applied at Baihui (GV 20), Dazhui (GV 14) and Shenting (GV 24); acupuncture at Jing-well points on the differentiated meridians was applied at corresponding Jing-well points according to pattern of syndrome; routine acupuncture was applied at Baihui (GV 20), Sishencong (EX-HN 1), etc. Acupuncture and moxibustion were given once a day, 6 times a week for 4 weeks. In the control group, donepezil was prescribed for oral administration, 5 mg each time, once a day for 4 weeks. Before and after treatment, the scores of mini mental state examination (MMSE) and activities of daily living (ADL) were observed, and the serum levels of AChE and VEGF were detected in the two groups. RESULTS: Compared before treatment, the MMSE and ADL scores and serum level of VEGF were increased (P<0.05), the serum level of AChE was decreased (P<0.05) after treatment in the two groups. The MMSE and ADL scores after treatment in the observation group were higher than the control group (P<0.05). CONCLUSION: Huayu Tongluo moxibustion combined with acupuncture at Jing-well points on the differentiated meridians and routine acupuncture could improve cognitive function and activities of daily living, which may be related to the regulation of serum levels of VEGF and AChE.