Functions of pancreatic beta cells and adipocytes in bombesin receptor subtype-3-deficient mice.
We previously reported that mice lacking bombesin receptor subtype-3 (BRS-3) exhibit mild late-onset obesity and glucose intolerance [Nature 390 (1997) 160]. To examine the mechanism by which glucose intolerance is developed in these mice, we studied insulin release and proinsulin biosynthesis in isolated pancreatic islets and glucose uptake and facilitative glucose transporter (GLUT)-4 translocation in adipose tissues. Although islet insulin contents and the size and number of islets of Langerhans in BRS-3-deficient mice decreased, there was no difference in glucose-stimulated insulin release and proinsulin biosynthesis between BRS-3-deficient and wild-type control mice. In contrast, adipose tissues exhibited a marked difference: the uptake of [(14)C]2-deoxy-D-glucose by adipocytes isolated from BRS-3-deficient mice was not stimulated by 10(-7)M insulin addition, and membrane fractionation analysis showed that GLUT4 was barely detected in the fraction of plasma membrane in BRS-3-deficient mice in the presence of 10(-7)M insulin. Quantitative reverse transcription-PCR (RT-PCR) showed that mRNA levels of GLUT4, insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2, syntaxin 4, SNAP23, and VAMP-2 in adipose tissues of BRS-3-deficient mice were unchanged compared with those in wild-type control mice. We concluded that impaired glucose metabolism observed in BRS-3-deficient mice was mainly caused by impaired GLUT4 translocation in adipocytes.
Nakamichi
Yoko
Y
Department of Biochemistry (II), Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan.
Wada
Etsuko
E
Aoki
Kumiko
K
Ohara-Imaizumi
Mica
M
Kikuta
Toshiteru
T
Nishiwaki
Chiyono
C
Matsushima
Satsuki
S
Watanabe
Takashi
T
Wada
Keiji
K
Nagamatsu
Shinya
S
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D015151:Immunoblotting; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D042541:Intracellular Space / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D011384:Proinsulin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018004:Receptors, Bombesin / Q000172:deficiency* / Q000235:genetics
D002250:Carbon Radioisotopes; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D018004:Receptors, Bombesin; C495693:Slc2a4 protein, mouse; C107120:bombesin receptor subtype 3; D011384:Proinsulin; D003847:Deoxyglucose; D005947:Glucose