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GESTATIONAL DIABETES MELLITUS (GDM) IS A DISEASE OF PREGNANCY THAT IS ASSOCIATED WITH D-GLUCOSE INTOLERANCE AND FOETO-PLACENTAL VASCULAR DYSFUNCTION. GMD CAUSES MITOCHONDRIAL DYSFUNCTION IN THE PLACENTAL ENDOTHELIUM AND TROPHOBLAST. ADDITIONALLY, GDM IS ASSOCIATED WITH REDUCED PLACENTAL OXIDATIVE PHOSPHORYLATION DUE TO DIMINISHED ACTIVITY OF THE MITOCHONDRIAL F0F1-ATP SYNTHASE (COMPLEX V). THIS PHENOMENON MAY RESULT FROM A HIGHER GENERATION OF REACTIVE SUPEROXIDE ANION AND NITRIC OXIDE. PLACENTAL MITOCHONDRIAL BIOGENESIS AND MITOPHAGY WORK IN CONCERT TO MAINTAIN CELL HOMEOSTASIS AND ARE VITAL MECHANISMS SECURING THE EFFICIENT GENERATION OF ATP, WHOSE DEMAND IS HIGHER IN PREGNANCY, ENSURING FOETAL GROWTH AND DEVELOPMENT. ADDITIONAL FACTORS DISTURBING PLACENTAL ATP SYNTHASE ACTIVITY IN GDM INCLUDE PRE-GESTATIONAL MATERNAL OBESITY OR OVERWEIGHT, INTRACELLULAR PH, MIRNAS, FATTY ACID OXIDATION, AND FOETAL (AND PLACENTAL) SEX. GDM IS ALSO ASSOCIATED WITH MATERNAL AND FOETAL HYPERINSULINAEMIA, ALTERED CIRCULATING LEVELS OF ADIPONECTIN AND LEPTIN, AND THE ACCUMULATION OF EXTRACELLULAR ADENOSINE. HERE, WE REVIEWED THE POTENTIAL INTERPLAY BETWEEN THESE MOLECULES OR METABOLIC CONDITIONS ON THE MECHANISMS OF MITOCHONDRIAL DYSFUNCTION IN THE FOETO-PLACENTAL UNIT IN GDM PREGNANCIES.

GESTATIONAL DIABETES MELLITUS (GDM) IS A DISEASE OF PREGNANCY ASSOCIATED WITH MATERNAL AND FOETAL HYPERGLYCAEMIA AND ALTERED FOETOPLACENTAL VASCULAR FUNCTION. HUMAN FOETOPLACENTAL MICROVASCULAR AND MACROVASCULAR ENDOTHELIUM FROM GDM PREGNANCY SHOW INCREASED MAXIMAL L-ARGININE TRANSPORT CAPACITY VIA THE HUMAN CATIONIC AMINO ACID TRANSPORTER 1 (HCAT-1) ISOFORM AND NITRIC OXIDE (NO) SYNTHESIS BY THE ENDOTHELIAL NO SYNTHASE (ENOS). THESE ALTERATIONS ARE PARALLELED BY LOWER MAXIMAL TRANSPORT ACTIVITY OF THE ENDOGENOUS NUCLEOSIDE ADENOSINE VIA THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1 (HENT1) AND ACTIVATION OF ADENOSINE RECEPTORS. A CAUSAL RELATIONSHIP HAS BEEN DESCRIBED FOR ADENOSINE-ACTIVATION OF A2A ADENOSINE RECEPTORS, HCAT-1, AND ENOS ACTIVITY (I.E. THE ADENOSINE/L-ARGININE/NITRIC OXIDE, ALANO, SIGNALLING PATHWAY). INSULIN RESTORES THESE ALTERATIONS IN GDM VIA ACTIVATION OF INSULIN RECEPTOR A (IR-A) FORM IN THE MACROVASCULAR BUT IR-A AND IR-B FORMS IN THE MICROCIRCULATION OF THE HUMAN PLACENTA. ADIPOKINES ARE SECRETED FROM ADIPOCYTES INFLUENCING THE FOETOPLACENTAL METABOLIC AND VASCULAR FUNCTION. VARIOUS ADIPOKINES ARE DYSREGULATED IN GDM, WITH ADIPONECTIN AND LEPTIN PLAYING MAJOR ROLES. ABNORMAL PLASMA CONCENTRATION OF THESE ADIPOKINES AND THE ACTIVATION OR THEIR RECEPTORS ARE INVOLVED IN THE PATHOPHYSIOLOGY OF GDM. HOWEVER, INVOLVEMENT OF ADIPOKINES, ADENOSINE, AND INSULIN RECEPTORS AND MEMBRANE TRANSPORTERS IN THE AETIOLOGY OF THIS DISEASE OF PREGNANCY IS UNKNOWN. THIS REVIEW FOCUSES ON THE PATHOPHYSIOLOGY OF INSULIN AND ADENOSINE RECEPTORS AND L-ARGININE AND ADENOSINE MEMBRANES TRANSPORTERS GIVING AN OVERVIEW OF THE KEY ADIPOKINES LEPTIN AND ADIPONECTIN IN THE FOETOPLACENTAL VASCULATURE IN GDM. THIS ARTICLE IS PART OF A SPECIAL ISSUE ENTITLED: MEMBRANE TRANSPORTERS AND RECEPTORS IN PREGNANCY METABOLIC COMPLICATIONS EDITED BY LUIS SOBREVIA.