BACKGROUND AND PURPOSE: Metformin is the oldest insulin sensitizer prescribed to type 2 diabetes (T2D) patients.
Other functions have been ascribed to Metformin including treatment of anovulatory infertility. However, Metformin effects on male reproduction remained unexplored. The Sertoli cell (SC) is crucial for germ cell development exerting a metabolic control of spermatogenesis. Herein we report the effect of Metformin on SC metabolism.
EXPERIMENTAL APPROACH: Rat SCs were cultured in Metformin presence (5, 50 and 500 μM) or absence. mRNA and protein levels of glucose transporters (GLUT1 and GLUT3), phosphofructokinase1 (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by qPCR and western blot, respectively. LDH activity was assessed and metabolite production/consumption was determined by 1 H-NMR.
KEY RESULTS: Pharmacological dose of Metformin (50 μM) decreases mRNA and protein levels of GLUT1, GLUT3 and MCT4. However, the glycolytic flux was increased as glucose consumption was maintained and LDH activity and lactate production increased. Our results suggest two mechanisms for Metformin action: 1) decrease of mRNA and protein levels of glycolysis-related transporters though increasing their activity, particularly in SCs exposed to a pharmacological dose; 2) antioxidant activity is achieved by alanine production stimulation, maintaining NADH/NAD+ equilibrium. No major metabolic cytotoxicity was detected in SCs exposed to Metformin supra-pharmacological concentration.
CONCLUSIONS AND IMPLICATIONS: Lactate produced by SCs provides nutritional support and has an antiapoptotic effect in the developing germ cells, thus our results provide evidence that Metformin may be considered as a good anti-diabetic agent for male T2D patients in reproductive age.
Written by:
Alves M, Martins A, Vaz C, Correia S, Moreira P, Oliveira P, Socorro S. Are you the author?
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
Reference: Br J Pharmacol. 2013 Nov 22. Epub ahead of print.
doi: 10.1111/bph.12522
PubMed Abstract
PMID: 24261663
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