PPAR-gamma overexpression suppresses glucose-induced proinsulin biosynthesis and insulin release synergistically with pioglitazone in MIN6 cells.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) regulates several cellular functions; however, its physiological role in pancreatic beta cell functions remains to be determined. In the present study, we investigated the synergistic effect of PPAR-gamma and its agonist, pioglitazone, on proinsulin biosynthesis and insulin release in a glucose-responsible insulinoma cell line, MIN6 cells. Expression of PPAR-gamma in MIN6 cells was not detectable by RT-PCR and immunoblot analysis. When PPAR-gamma-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 beta cell function in control MIN6 cells, although pioglitazone synergistically augmented the inhibitory effect of PPAR-gamma on proinsulin biosynthesis and insulin release under the condition of PPAR-gamma overexpression. Our results demonstrate that PPAR-gamma plays a negative role in pancreatic beta cells.
Nakamichi
Yoko
Y
Department of Biochemistry (II), Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan.
Kikuta
Toshiteru
T
Ito
Eisuke
E
Ohara-Imaizumi
Mica
M
Nishiwaki
Chiyono
C
Ishida
Hitoshi
H
Nagamatsu
Shinya
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D000077205:Pioglitazone; D011384:Proinsulin / Q000096:biosynthesis*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000502:physiology*
D018076:DNA, Complementary; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D012313:RNA; D011384:Proinsulin; D005947:Glucose; D000077205:Pioglitazone