The AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribonucleoside, regulates lactate production in rat Sertoli cells

Abstract

The aim of the present study was to investigate whether the AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in Sertoli cells and whether its activation by 5-aminoimidazole-4-carboxamide-1-b-Dribonucleoside (AICAR) results in the regulation of cell metabolism to ensure lactate supply for germ cell development. Sertoli cell cultures from 20-day-old rats were used. Western blot analysis for the a-subunit of AMPK showed that high levels of AMPK are present in Sertoli cells. Treatment of the cultures with AICAR resulted in a dose-and time-dependent increase of P-AMPK levels indicating activation of the enzyme. A possible effect of AICAR on Sertoli cell lactate production was then analyzed. A dose-and time-dependent increment in lactate secretion was observed. The participation of AMPK activation in different biochemical processes that may be implicated in the regulation of lactate production was also analyzed. AICAR stimulated glucose uptake in a dose-and time-dependent manner. Additionally, AICAR increased the glucose transporter 1 (GLUT1) and decreased the glucose transporter 3 (GLUT3) mRNA levels. As for the role of AMPK in the regulation of the monocarboxylate transporters 1 and 4 (MCT1 and MCT4), it has been observed that AICAR treatment decreased MCT1 and increased MCT4 mRNA levels. In summary, the results presented herein show that AMPK is present in Sertoli cells and that its activation by AICAR increases lactate production as a result, at least in part, of a) an increase in glucose uptake, b) an increase in GLUT1 expression, and c) a decrease in MCT1 and an increase in MCT4 levels. Altogether, these results suggest an important role of AMPK in modulating the nutritional function of Sertoli cells.

The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations

“…Previous studies on rat and mice demonstrated the presence of AMPK in testis (Cheung et al 2000, Galardo et al 2007, Tartarin et al 2012b. In the chicken testis, both AMPKα, AMPKβ and the AMPKγ1 subunit were localised in the seminiferous tubules.…”

“…Interestingly, activation of the AMPK pathway by another pharmacological drug (AICAR) in rat Sertoli cells stimulated lactate production (Galardo et al 2007). Under our conditions, the lactate production could be due to the role of metformin in inhibiting the respiratory chain complex 1, blocking mitochondrial activity (Leverve et al 2003) and promoting anaerobic respiration (Rena et al 2013).…”

AMP-activated protein kinase regulates the expression of monocarboxylate transporter 4 in skeletal muscle

“…MCT4 plays a critical role in lactic acid efflux from skeletal muscle and is essential for muscle homeostasis. In rat primary sertoli cells, it has been reported that AICAR treatment increased MCT4 mRNA level and lactic acid production (Galardo et al 2007). However, the involvement of AMPK in MCT4 regulation in skeletal muscle is not clear.…”

L’AMPK, régulateur de l’énergie et des fonctions des spermatozoïdes

“…spermatogenèse, dans les cellules de Leydig 2 et dans les cellules de Sertoli 3 [19][20][21]. Dans les cellules de Sertoli, la voie de signalisation AMPK/mTOR (mammalian target of rapamycin) participe à la régulation de l'autophagie et de l'apoptose induite par des substances toxiques [24].…”