Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats

Takeshi Hara, Aya Koda, Naoko Nozawa, Urara Ota, Hikaru Kondo, Hitoshi Nakagawa, Atsuko Kamiya, Kazutoshi Miyashita, Hiroshi Itoh, Motowo Nakajima, Tohru Tanaka

Research output: Contribution to journalArticle

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Abstract

Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). 5-Aminolevulinic acid (ALA), a natural amino acid produced only in the mitochondria, is a precursor of heme. Cytochromes that contain heme play an important role in aerobic energy metabolism. Thus, ALA may help reduce T2DM-associated hyperglycemia. In this study, we investigated the effect of ALA combined with sodium ferrous citrate (SFC) on hyperglycemia in Zucker diabetic fatty (ZDF) rats. We found that the gavage administration of ALA combined with SFC (ALA/SFC) for 6 weeks reduced plasma glucose and hemoglobin A1c (HbA1c) levels in rats without affecting plasma insulin levels. The glucose-lowering effect depended on the amount of ALA/SFC administered per day. Furthermore, the glucose tolerance was also significantly improved by ALA/SFC administration. Although food intake was slightly reduced in the rats administered ALA/SFC, there was no effect on their body weight. Importantly, ALA/SFC administration induced heme oxygenase-1 (HO-1) expression in white adipose tissue and liver, and the induced expression levels of HO-1 correlated with the glucose-lowering effects of ALA/SFC. Taken together, these results suggest that ALA combined with ferrous ion is effective in reducing hyperglycemia of T2DM without affecting plasma insulin levels. HO-1 induction may be involved in the mechanisms underlying the glucose-lowering effect of ALA/SFC. Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). Various heme-containing cytochromes contribute to aerobic energy metabolism and 5-aminolevulinic acid (ALA), a natural amino acid, is a precursor of heme. We have found that the administration of ALA combined with ferrous ion can effectively reduce hyperglycemia of T2DM.

Original languageEnglish
Pages (from-to)515-528
Number of pages14
JournalFEBS Open Bio
Volume6
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

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Aminolevulinic Acid
Rats
Hemoglobins
Ions
Plasmas
Glucose
Sodium
Medical problems
Type 2 Diabetes Mellitus
Heme
Hyperglycemia
Heme Oxygenase-1
Cytochromes
Energy Metabolism
Insulin
monoferrous acid citrate
sodium citrate
Amino Acids
White Adipose Tissue
Mitochondria

Keywords

  • 5-aminolevulinic acid
  • Heme oxygenase-1
  • Mitochondria
  • Sodium ferrous citrate
  • Type 2 diabetes mellitus
  • Zucker diabetic fatty rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats. / Hara, Takeshi; Koda, Aya; Nozawa, Naoko; Ota, Urara; Kondo, Hikaru; Nakagawa, Hitoshi; Kamiya, Atsuko; Miyashita, Kazutoshi; Itoh, Hiroshi; Nakajima, Motowo; Tanaka, Tohru.

In: FEBS Open Bio, Vol. 6, No. 6, 01.06.2016, p. 515-528.

Research output: Contribution to journalArticle

Hara, T, Koda, A, Nozawa, N, Ota, U, Kondo, H, Nakagawa, H, Kamiya, A, Miyashita, K, Itoh, H, Nakajima, M & Tanaka, T 2016, 'Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats', FEBS Open Bio, vol. 6, no. 6, pp. 515-528. https://doi.org/10.1002/2211-5463.12048
Hara, Takeshi ; Koda, Aya ; Nozawa, Naoko ; Ota, Urara ; Kondo, Hikaru ; Nakagawa, Hitoshi ; Kamiya, Atsuko ; Miyashita, Kazutoshi ; Itoh, Hiroshi ; Nakajima, Motowo ; Tanaka, Tohru. / Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats. In: FEBS Open Bio. 2016 ; Vol. 6, No. 6. pp. 515-528.
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abstract = "Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). 5-Aminolevulinic acid (ALA), a natural amino acid produced only in the mitochondria, is a precursor of heme. Cytochromes that contain heme play an important role in aerobic energy metabolism. Thus, ALA may help reduce T2DM-associated hyperglycemia. In this study, we investigated the effect of ALA combined with sodium ferrous citrate (SFC) on hyperglycemia in Zucker diabetic fatty (ZDF) rats. We found that the gavage administration of ALA combined with SFC (ALA/SFC) for 6 weeks reduced plasma glucose and hemoglobin A1c (HbA1c) levels in rats without affecting plasma insulin levels. The glucose-lowering effect depended on the amount of ALA/SFC administered per day. Furthermore, the glucose tolerance was also significantly improved by ALA/SFC administration. Although food intake was slightly reduced in the rats administered ALA/SFC, there was no effect on their body weight. Importantly, ALA/SFC administration induced heme oxygenase-1 (HO-1) expression in white adipose tissue and liver, and the induced expression levels of HO-1 correlated with the glucose-lowering effects of ALA/SFC. Taken together, these results suggest that ALA combined with ferrous ion is effective in reducing hyperglycemia of T2DM without affecting plasma insulin levels. HO-1 induction may be involved in the mechanisms underlying the glucose-lowering effect of ALA/SFC. Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). Various heme-containing cytochromes contribute to aerobic energy metabolism and 5-aminolevulinic acid (ALA), a natural amino acid, is a precursor of heme. We have found that the administration of ALA combined with ferrous ion can effectively reduce hyperglycemia of T2DM.",
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AU - Ota, Urara

AU - Kondo, Hikaru

AU - Nakagawa, Hitoshi

AU - Kamiya, Atsuko

AU - Miyashita, Kazutoshi

AU - Itoh, Hiroshi

AU - Nakajima, Motowo

AU - Tanaka, Tohru

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