PMID- 37560982 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20231102 IS - 1872-8081 (Electronic) IS - 0951-6433 (Linking) VI - 49 IP - 5 DP - 2023 Sep-Oct TI - miR-34a/SIRT1/HIF-1alpha axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise. PG - 1085-1098 LID - 10.1002/biof.1979 [doi] AB - Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1alpha pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1alpha levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1alpha (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1alpha (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1alpha (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1alpha proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1alpha pathway. CI - (c) 2023 International Union of Biochemistry and Molecular Biology. FAU - Sarlak, Zeynab AU - Sarlak Z AD - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. FAU - Eidi, Akram AU - Eidi A AD - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. FAU - Ghorbanzadeh, Vajihe AU - Ghorbanzadeh V AUID- ORCID: 0000-0002-4195-3516 AD - Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Moghaddasi, Mehrnoush AU - Moghaddasi M AD - Razi Herbal Medicines Research Center, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Mortazavi, Pejman AU - Mortazavi P AD - Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran, Iran. LA - eng PT - Journal Article DEP - 20230810 PL - Netherlands TA - Biofactors JT - BioFactors (Oxford, England) JID - 8807441 RN - 0 (MicroRNAs) RN - 107-92-6 (Butyric Acid) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Rats MH - Animals MH - *MicroRNAs/genetics/metabolism MH - *Diabetes Mellitus, Experimental/genetics MH - Butyric Acid/pharmacology MH - Sirtuin 1/genetics/metabolism MH - *Diabetes Mellitus, Type 2/genetics OTO - NOTNLM OT - FOXO1 OT - HIF-1alpha OT - SIRT1 OT - angiogenesis OT - miR-34a OT - sodium butyrate OT - treadmill exercise OT - type 2 diabetes mellitus EDAT- 2023/08/10 12:42 MHDA- 2023/08/10 12:43 CRDT- 2023/08/10 09:33 PHST- 2023/02/19 00:00 [received] PHST- 2023/05/11 00:00 [accepted] PHST- 2023/08/10 12:43 [medline] PHST- 2023/08/10 12:42 [pubmed] PHST- 2023/08/10 09:33 [entrez] AID - 10.1002/biof.1979 [doi] PST - ppublish SO - Biofactors. 2023 Sep-Oct;49(5):1085-1098. doi: 10.1002/biof.1979. Epub 2023 Aug 10.