title: Type 2 diabetic conditions in Otsuka Long-Evans Tokushima Fatty rats are ameliorated by 5-aminolevulinic acid.
abstract: A precursor of protoporphyrin IX, 5-aminolevulinic acid (5-ALA) is used as a prodrug for photodiagnosis and photodynamic therapy. Recently, it has been shown that 5-ALA reduces glucose levels during fasting and after glucose loading in prediabetic subjects. We hypothesized that 5-ALA ameliorates diabetic conditions through mitochondrial changes in visceral adipose tissue. In order to explore the metabolic effects on the type 2 diabetic state, we administered ALA hydrochloride in combination with sodium ferrous citrate to Otsuka Long-Evans Tokushima Fatty (OLETF) rats at intragastric doses of 20 and 300 mg kg(-1) d(-1) for 6 weeks. The administration of 300 mg kg(-1) d(-1) of 5-ALA improved glucose intolerance, hypertriglyceridemia, and hyperleptinemia in OLETF rats more effectively than the administration of an equivalent dose of metformin, in accordance with reductions in food intake and body weight. Furthermore, the weight of the retroperitoneal fat tended to decrease and cellular mitochondrial content of the fat was markedly reduced by the 5-ALA administration, showing a positive correlation. These results suggest that 5-ALA ameliorates diabetic abnormalities in OLETF rats by reducing the visceral fat mass and mitochondrial content of adipocytes in a site-specific manner.
authors.affiliation: Biomaterial in Tokyo Co, Ltd, Tokyo, Japan; Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yasuzawa
authors.affiliation: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Uesaka
authors.affiliation: Biomaterial in Tokyo Co, Ltd, Tokyo, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: SBI Pharmaceuticals Co, Ltd, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: SBI Pharmaceuticals Co, Ltd, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kuwahata
authors.affiliation: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan. Electronic address: kido@kpu.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kido
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D013393:Sucrase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; D000622:Aminolevulinic Acid; D002784:Cholesterol; D013393:Sucrase
keywords: 5-Aminolevulinic acid; Mitochondria; OLETF rat; Type 2 diabetes mellitus; Visceral fat