Expression and distribution of lactate/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas

Transport of lactate across the plasma membrane of pancreatic islet beta -c ells is slow, as described by Sekine et al. (J Biol Chem 269:4895-4902, 199 4), which is a feature that may be important for normal nutrient-induced in sulin secretion. Although eight members of the monocarboxylate transporter (MCT) family have now been identified, the expression of these isoforms wit hin the exocrine and endocrine pancreas has not been explored in detail. Us ing immunocytochemical analysis of pancreatic sections fixed in situ, we de monstrated three phenomena. First, immunoreactivity of the commonly express ed lactate transporter isoform MCT1 is near zero in both alpha- and beta -c ells but is abundant in the pancreatic acinar cell plasma membrane. No MCT2 or MCT4 was detected in any pancreatic cell type. Second, Western analysis of purified beta- and non-beta -cell membranes revealed undetectable level s of MCT1 and MCT4. In derived beta -cell lines, MCT1 was absent from MING cells and present in low amounts in INS-1 cell membranes and at high levels in RINm5F cells. MCT4 was weakly expressed in MIN6 beta -cells. Third, CD1 47, an MCT-associated chaperone protein, which is closely colocalized with MCT1 on acinar cell membranes, was absent from islet cell membranes. CD147 was also largely absent from MIN6 and INS-1 cells but abundant in RINm5F ce lls. Low expression of MCT1, MCT2, and MCT4 contributes to the enzymatic co nfiguration of beta -cells, which is poised to ensure glucose oxidation and the generation of metabolic signals and may also be important for glucose sensing in islet non-beta -cells. MCT overexpression throughout the islet c ould contribute to deranged hormone secretion in some forms of type 2 diabe tes.