Protection from diabetes-induced atherosclerosis and renal disease by d-carnosine-octylester: effects of early vs late inhibition of advanced glycation end-products in Apoe-null mice

Menini, Stefano; Iacobini, Carla; Ricci, C; Fantauzzi, Claudia Blasetti; Pugliese, Giuseppe

doi:10.1007/s00125-014-3467-6

Cited by 61 publications

(54 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The clinical importance becomes apparent when realizing that ACE-inhibitors still are the only medication for diabetic patients with nephropathy in order to delay progression. A very recent study on D-carnosine-octylester (a bioavailable carnosine-derivate) in STZ treated diabetic ApoE-null mice displayed similar findings with reduced renal hypertrophy and albuminuria, but no effect on cholesterol36. As glycemic control remained unaffected in this model, we speculate that at least part of the renoprotection is mediated by carnosine, whereas the insulinotropic effect may be mediated by histamine and β-alanine.…”

Section: Discussionsupporting

confidence: 78%

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Albrecht

Schilperoort

Zhang

et al. 2017

Sci Rep

114

View full text Add to dashboard Cite

We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman’s capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes.

show abstract

Section: Discussionsupporting

confidence: 78%

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Albrecht

Schilperoort

Zhang

et al. 2017

Sci Rep

114

View full text Add to dashboard Cite

show abstract

“…Oxidative stress, reflected by increased cellular oxidation reactions and decreased reduction reactions (Banerjee and Vats, 2013), has a close relationship with HG-induced vascular injury (Battelli et al , 2014, Menini et al , 2014, Thallas-Bonke et al , 2014.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates high glucose-induced oxidative stress injury in human umbilical vein endothelial cells by activating AMPK

Zhou

Gao

et al. 2015

Life Sciences

View full text Add to dashboard Cite

“…We therefore provide a new mechanism by which carnosine improves the metabolic control in diabetes and protect against the development of complications in diabetes. Even though carnosine shown protective effect in several animal models for complications of diabetes (Pfister et al 2011, Riedl et al 2011, Ansurudeen et al 2012, Yapislar & Aydogan 2012, Brown et al 2014, Peters et al 2014, Menini et al 2015 and strongly suggested to be relevant for diabetes complications in humans (Ahluwalia et al 2011, Kurashige et al 2013) the exact mechanism of action is still unraveled. Here we suggest a potential mechanism by showing that carnosine complexly modulates IGFBP1 by different mechanisms, i.e.…”

Section: Discussionmentioning

confidence: 99%

Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1

Forsberg¹,

Botusan²,

Wang³

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1a) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expression Igfbp1, through a complex mechanism acting both directly by suppressing the HIF-1a-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes.

show abstract

Protection from diabetes-induced atherosclerosis and renal disease by d-carnosine-octylester: effects of early vs late inhibition of advanced glycation end-products in Apoe-null mice

Cited by 61 publications

References 36 publications

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

Resveratrol ameliorates high glucose-induced oxidative stress injury in human umbilical vein endothelial cells by activating AMPK

Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1

Contact Info

Product

Resources

About