PMID- 9186301
OWN - NLM
STAT- MEDLINE
DCOM- 19970707
LR  - 20190725
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 46
IP  - 6
DP  - 1997 Jun
TI  - Retinoid-X receptors and the effects of 9-cis-retinoic acid on insulin secretion 
      from RINm5F cells.
PG  - 656-60
AB  - Retinoid-X receptors (RXRs) are 9-cis-retinoic acid (9CRA)-dependent gene 
      transcription factors, which modulate the action of all-trans-retinoic acid 
      (ATRA), fatty acids, thyroid hormone (TH), and vitamin D (VD) by forming dimers 
      with themselves or ATRA, TH, peroxisome proliferator activator receptors (PPARs), 
      or VD receptors (VDRs). To determine if 9CRA and RXRs have a role in secretion, 
      RINm5F cells were assayed for RXR transcripts and effects of 9CRA and ATRA on 
      secretion. A single RXR alpha transcript and two RXR beta transcripts, but not 
      RXR gamma, were evident by Northern blot. Cells were cultured for 48 hours 
      without and with 9CRA 1 to 1,000 nmol/L and then stimulated with glucose 0, 0.5, 
      2.8, 7, and 11 mmol/L 9CRA increased secretion at each glucose concentration, 
      9CRA increased secretion by 50% to 100% (ANOVA, P < .001) with consistent 
      concentration-dependent responses (eg. at glucose 2.8 mmol/L 9CRA: 0 nmol/L, 5.02 
      +/- .20 ng/(10(6) cells.h); 1 nmol/L, 6.97 +/- .30; 10 nmol/L, 8.36 +/- .18; 100 
      nmol/L, 9.15 +/- .28; 1,000 nmol/L, 10.24 +/- .24; n = 6). Although RINm5F cells 
      respond slightly if at all to glucose, 9CRA facilitated glucose-induced insulin 
      release (eg, at 9CRA 100 nmol/L, glucose: 0.5 mmol/L, 7.47 +/- .22 ng/(10(6) 
      cells.h); 2.8 mmol/L, 9.15 +/- .27; 7 mmol/L, 9.81 +/- .19; 11 mmol/L, 11.16 +/- 
      .23; n = 6). ATRA increased secretion by 28% to 57% (ANOVA, P < .001: at glucose 
      2.8 mmol/L, ATRA: 0 nmol/L, 6.17 +/- .32 ng/(10(6) cells.h); 1 nmol/L, 7.91 +/- 
      .29; 10 nmol/L, 9.75 +/- .14; 100 nmol/L, 9.66 +/- .33; n = 6). 9CRA was more 
      potent than ATRA (eg, at 2.8 mmol/L; baseline, 8.17 +/- .32 ng/(10(8) cells.h); 
      ATRA 100 nmol/L, 9.66 +/- .33; 9CRA 100 nmol/L, 10.81 +/- .15; P < .05, n = 6). 
      When 9CRA was combined with ATRA, the combination was not additive or synergistic 
      (eg, at 2.8 mmol/L: ATRA 100 nmol/L, 9.66 +/- .33 ng/(10(6) cells.h); 9CRA 100 
      nmol/L, 10.81 +/- .15; ATRA 100 nmol/L + 9CRA 100 nmol/L, 10.79 +/- .28; P < .05, 
      n = 6). These studies show that (1) 9CRA stimulates insulin secretion from RINm5F 
      cells. This effect appears to be at least equal to if not greater than that 
      observed with ATRA, but additive or synergistic effects with ATRA were not 
      evident; (2) 9CRA may facilitate glucose-induced release; and (3) multiple RXR 
      transcripts are present in insulin-secreting cells, implying specific functions. 
      Our findings support the idea that the effects of 9CRA on insulin secretion are 
      mediated through RXR homodimers or heterodimers with retinoic acid receptors 
      (RARs) or possibly other nuclear receptors. Retinoid deficiency or alterations in 
      retinoid receptor function could lead to abnormalities of cell growth or 
      secretion.
FAU - Chertow, B S
AU  - Chertow BS
AD  - Research and Medical Service, Huntington Veterans Affairs Medical Center, WV, 
      USA.
FAU - Driscoll, H K
AU  - Driscoll HK
FAU - Goking, N Q
AU  - Goking NQ
FAU - Primerano, D
AU  - Primerano D
FAU - Cordle, M B
AU  - Cordle MB
FAU - Matthews, K A
AU  - Matthews KA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Insulin)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Alitretinoin
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Line
MH  - Dimerization
MH  - Drug Interactions
MH  - Glucose/pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans
MH  - Receptors, Retinoic Acid/*biosynthesis/physiology
MH  - Retinoid X Receptors
MH  - Transcription Factors/*biosynthesis/physiology
MH  - Transcription, Genetic
MH  - Tretinoin/*pharmacology
EDAT- 1997/06/01 00:00
MHDA- 1997/06/01 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/06/01 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
AID - S0026-0495(97)90009-3 [pii]
AID - 10.1016/s0026-0495(97)90009-3 [doi]
PST - ppublish
SO  - Metabolism. 1997 Jun;46(6):656-60. doi: 10.1016/s0026-0495(97)90009-3.