scholarly journals Organic Cation Transporter 1 Polymorphisms Predict the Metabolic Response to Metformin in Women with the Polycystic Ovary Syndrome

2010 ◽  
Vol 95 (10) ◽  
pp. E204-E208 ◽  
Author(s):  
Alessandra Gambineri ◽  
Federica Tomassoni ◽  
Daniela Ibarra Gasparini ◽  
Antonio Di Rocco ◽  
Vilma Mantovani ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Organic Cation ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Organic Cation Transporter ◽  
Ovary Syndrome ◽  
Organic Cation Transporter 1

scholarly journals Association between Polymorphisms of OCT1 and Metabolic Response to Metformin in Women with Polycystic Ovary Syndrome

2019 ◽  
Vol 20 (7) ◽  
pp. 1720 ◽  
Author(s):  
Hui Chang ◽  
Yuan-Shuo Hsueh ◽  
Yung Cheng ◽  
Huang-Tz Ou ◽  
Meng-Hsing Wu
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Treatment Effectiveness ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Organic Cation Transporter ◽  
Oral Glucose ◽  
Metformin Treatment ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Insulin Sensitizer

Insulin-sensitizer treatment with metformin is widely used in polycystic ovary syndrome (PCOS). However, the treatment effectiveness shows individual differences in PCOS patients. Organic cation transporter (OCT) 1 and 2 have been reported to mediate metformin transport in the liver and kidney, respectively. In this study, we investigated the association between the polymorphisms of OCT1 and OCT2 and the treatment effectiveness of metformin in PCOS patients. The single nucleotide polymorphisms (SNPs) of OCT1 (rs683369 and rs628031) and OCT2 (rs316019) were analyzed in 87 PCOS and 113 control women. Oral glucose tolerance tests (OGTTs), which represented metformin treatment response, were conducted at the start of treatment and after six-month treatment. The results demonstrated that the SNP frequencies of OCT1 and OCT2 were not associated with PCOS pathophysiology, and that the polymorphisms of OCT1 and OCT2 were not associated with the OGTT parameters at baseline. However, PCOS patients with the G allele of OCT1 rs683369 and/or with the A allele of OCT1 rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment. Moreover, the interactions of metformin*SNP were significant in both OCT1 rs683369 (p < 0.001) and rs628031 (p = 0.001) during the treatment period. Taken together, genetic polymorphisms of OCT1 contributed to different metformin treatment responses, and further study is needed to establish personalized treatment programs using a pharmacogenomic algorithm approach in PCOS patients.

Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

2015 ◽  
Vol 82 (6) ◽  
pp. 885-891 ◽  
Author(s):  
Mehri Jamilian ◽  
Maryamalsadat Razavi ◽  
Zohreh Fakhrie Kashan ◽  
Yasser Ghandi ◽  
Tayebeh Bagherian ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Selenium Supplementation ◽  
Ovary Syndrome ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Metformin Inhibits Human Androgen Production by Regulating Steroidogenic Enzymes HSD3B2 and CYP17A1 and Complex I Activity of the Respiratory Chain

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4354-4366 ◽  
Author(s):  
Andrea Hirsch ◽  
Dagmar Hahn ◽  
Petra Kempná ◽  
Gaby Hofer ◽  
Jean-Marc Nuoffer ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Polycystic Ovary Syndrome ◽  
Respiratory Chain ◽  
Complex I ◽  
Organic Cation ◽  
Polycystic Ovary ◽  
Organic Cation Transporters ◽  
Ovary Syndrome ◽  
Ampk Signaling ◽  
Cation Transporters

Metformin is treatment of choice for the metabolic consequences seen in polycystic ovary syndrome for its insulin-sensitizing and androgen-lowering properties. Yet, the mechanism of action remains unclear. Two potential targets for metformin regulating steroid and glucose metabolism are AMP-activated protein kinase (AMPK) signaling and the complex I of the mitochondrial respiratory chain. Androgen biosynthesis requires steroid enzymes 17α-Hydroxylase/17,20 lyase (CYP17A1) and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2), which are overexpressed in ovarian cells of polycystic ovary syndrome women. Therefore, we aimed to understand how metformin modulates androgen production using NCI-H295R cells as an established model of steroidogenesis. Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities. The effect of metformin on androgen production was dose dependent and subject to the presence of organic cation transporters, establishing an important role of organic cation transporters for metformin's action. Metformin did not affect AMPK, ERK1/2, or atypical protein kinase C signaling. By contrast, metformin inhibited complex I of the respiratory chain in mitochondria. Similar to metformin, direct inhibition of complex I by rotenone also inhibited HSD3B2 activity. In conclusion, metformin inhibits androgen production by mechanisms targeting HSD3B2 and CYP17-lyase. This regulation involves inhibition of mitochondrial complex I but appears to be independent of AMPK signaling.

scholarly journals Metabolic Response to Short-term Protein Supplementation in Reproductive-Aged Women with Polycystic Ovary Syndrome (PCOS) (P08-070-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Manisha Rao ◽  
Emily Zumbro ◽  
Morgan Dixon ◽  
Kayleigh Kaiser ◽  
Lily Sebastian ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
G Protein ◽  
Whey Protein ◽  
Repeated Measures ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Vital Role ◽  
Protein Supplementation ◽  
Oral Glucose ◽  
Ovary Syndrome

Abstract Objectives Women with polycystic ovary syndrome (PCOS) are commonly insulin resistant, hyperinsulinemic and hyperglycemic, increasing their risk for development of other metabolic, cardiovascular and reproductive disturbances. Dietary whey protein may attenuate postprandial glycemic excursions due to its effect on the gut-brain axis. The aim of the study is to evaluate 7-day whey protein supplementation on metabolic parameters in young women with PCOS. Methods A repeated measures (RM) design was used. Three women with and six without PCOS (PCO and CON respectively) underwent three 150-min oral glucose tolerance tests (OGTT): (i) OGTT without protein preload, (ii) OGTT on first and (iii) seventh day of protein preload. Participants consumed 35 g protein daily with protein intake 30 min before carbohydrate load on the test days. Blood samples collected at −30 (fasting/pre-preload), 0 (pre-glucose), 15, 30, 60, 90, 120 and 150 min of OGTTs were analyzed for glucose, insulin, and incretins. (Participant recruitment, data collection and analyses in progress.) Results Mixed design RM - MANOVA indicates that day of test and time did not have a significant effect on glucose levels within and between groups (P ≥ .05). However, day (P = .027) and time (P = .047) had a significant impact on insulin concentrations in both, PCO and CON groups. Insulin was significantly higher at 30 min compared to −30 and 0 min timepoints (P = .016 and P = .032 respectively) on the first and seventh days of preload. Conclusions An insulinogenic response elicited by 35 g protein preload may blunt glycemic responses, moderating them throughout the test period in women with PCOS and age-matched healthy controls. Timing of supplementation may play a vital role in achieving long term glucose homeostasis in PCOS. Funding Sources Texas Woman's University Research Enhancement Program & Glanbia Nutritionals, Inc.

Sign in / Sign up

Export Citation Format

Share Document