Abstract
Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates several cellular functions; however, its physiological role in pancreatic β cell functions remains to be determined. In the present study, we investigated the synergistic effect of PPAR-γ and its agonist, pioglitazone, on proinsulin biosynthesis and insulin release in a glucose-responsible insulinoma cell line, MIN6 cells. Expression of PPAR-γ in MIN6 cells was not detectable by RT-PCR and immunoblot analysis. When PPAR-γ-1 was overexpressed adenovirally in MIN6 cells, glucose-stimulated proinsulin biosynthesis and insulin release were inhibited. Pioglitazone treatment alone had no effects on these parameters of β cell function in control MIN6 cells, although pioglitazone synergistically augmented the inhibitory effect of PPAR-γ on proinsulin biosynthesis and insulin release under the condition of PPAR-γ overexpression. Our results demonstrate that PPAR-γ plays a negative role in pancreatic β cells.
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