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

Abstract

Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2 DM ). 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 T2 DM ‐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 T2 DM without affecting plasma insulin levels. HO ‐1 induction may be involved in the mechanisms underlying the glucose‐lowering effect of ALA / SFC .

Combination of 5‐aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft‐versus‐host disease

“…HO‐1 has antioxidant activity by bilirubin production, resulting in decreased ROS, and therefore prevents oxidative stress‐induced cellular damage in various tissues including the liver . In fact, the upregulation of HO‐1 has been shown to improve glucose metabolism, and enhance insulin signalling in several animal models of diabetes, which in turn was linked to antioxidant mechanisms . 5‐ALA/SFC produced by haem induces carbon monoxide in mouse kidney by activating HO‐1, demonstrating that 5‐ALA/SFC induces HO‐1 activity.…”

“…Porphyrinogens, precursors of protoporphyrin IX (PpIX) and haem were polymerized by eight molecules of 5‐ALA. Protoporphyrin IX is used in cancer treatment to identify and destroy tumors by photodynamic diagnosis and therapy . The insertion of ferrous ion into PpIX generates haem in the mitochondria .…”

Dietary 5-aminolevulinic acid enhances adenosine triphosphate production, ecdysis and immune response in Pacific white shrimp, Litopenaeus vannamei (Boone)

“…On the other hand, for reasons that are not clear, the group with the highest 5-ALA concentration (ALA60) had the lowest final weight. One possibility is that high concentration of 5-ALA may have slightly reduced food intake, as was reported in rats (Hara et al, 2016) and…”

“…5‐aminolevulinic acid (5‐ALA) is an endogenous nonprotein amino acid produced by the condensation of succinyl‐CoA and amino acid glycine by the action of aminolevulinic acid synthase (ALAS, EC 2.3.1.37) in the mitochondria (Fujii et al., ). It is also the sole initial material in the synthesis of haem in animal cells in vivo (Hara et al., ). Haem is a prosthetic group that interacts with different apoproteins to form functional haemoproteins (Kumar & Bandyopadhyay, ).…”

5‐ALA/SFC enhances HO‐1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis

“…Induction of apoptosis was mediated by the mitochondrial status, balance of pro-apoptotic and antiapoptotic molecules, and caspase activation. CsA-induced renal dysfunction and morphological changes were associated with mitochondrial damage in the kidneys [20]. Furthermore, CsA induced apoptosis of the renal proximal tubule cells in vitro through mitochondrial-dependent and mitochondrial-independent pathways as well as partially through activation of caspase-3 and oxidative stress [21].…”