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Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis

, : Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis. British Journal of Pharmacology 166(3): 1183-1191

Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms causing its functional dysfunction are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. Experimental approach. Blood lactate, pH and bicarbonate ion (HCO3?) levels were evaluated during continuous administration of 3 mg mL?1 metformin in drinking water using Mate1 knockout (?/?), heterozygous (+/?) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 4 mg kg?1 metformin orally. Furthermore, blood lactate data was obtained from diabetic patients given metformin.Key results. At seventh day after metformin administration in drinking water, significant high blood lactate, low pH and HCO3?levels were observed in Mate1?/? mice, but not in Mate1+/? mice. The blood lactate levels were not influenced in patients with heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after the metformin administration at a dose of 4 mg kg?1, the hepatic concentration of metformin was markedly higher in Mate1?/? mice than Mate1+/+ mice. and Implications. MATE1 dysfunction caused a remarkable elevation of the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.


PMID: 22242910

DOI: 10.1111/j.1476-5381.2012.01853.x

Other references

Yamaji, K., 2017: Immunoadsorption for collagen and rheumatic diseases. The field of therapeutics has seen remarkable progress in the recent years, which has made mainstream drug treatment possible for collagen and rheumatic diseases. However, treatment of intractable cases where drug effectiveness is poor is a challe...

Klotz, O., 1917: Symbols. Science 46(1189): 360-361

Kianmehr, A.; Mohammadi, H.Shahbaz.; Shokrgozar, M.Ali.; Omidinia, E., 2015: In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy. The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with ap...

Subtelny, A.O.; Hartman, M.C.T.; Szostak, J.W., 2008: Ribosomal synthesis of N-methyl peptides. N-Methyl amino acids (N-Me AAs) are a common component of nonribosomal peptides (NRPs), a class of natural products from which many clinically important therapeutics are obtained. N-Me AAs confer peptides with increased conformational rigidity, m...

O'Dwyer, D.N.; Armstrong, M.E.; Cooke, G.; Dodd, J.D.; Veale, D.J.; Donnelly, S.C., 2014: Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD). Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortalit...

Udintsev G.B.; Dmitriev L.V. (Dmitriyev L.V., 1975: Ultrabasic rocks of the ocean floor and the role of rift-zone ultrabasites. Pages 186-204 1975

Ljunghall, S.; Lind, L.; Lithell, H.; Skarfors, E.; Selinus, I.; Sørensen, O.H.; Wide, L., 1987: Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study. Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)2D3) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum...

Piva, M., 1966: Considerations on a case of pedunculated intracavitary thrombus of the right ventricle. Cardiologia Pratica 17(1): 61-74

Zyrianov, A.I., 1969: Significance of different methods of arrangement of the Foges-Proskauer test. Laboratornoe Delo 2: 119-119

Kayaba, Yuji; Fukuda, Yasuichiro; Komuro, Issei; Yanagisawa, Masashi; Kuwaki, Tomoyuki, 2003: Role of orexin in defense reaction and blood pressure regulation. Orexin is a newly identified hypothalamic neuropeptide, and has been thought to participate in cardiovascular regulation because of morphological characteristics and its pressor effect when exogenously applied. On the other hand, perifornical area...