REGULATION OF HUMAN INSULIN GENE-TRANSCRIPTION BY GLUCOSE, EPINEPHRINE, AND SOMATOSTATIN

被引:35
作者
REDMON, JB
TOWLE, HC
ROBERTSON, RP
机构
[1] UNIV MINNESOTA,SCH MED,DEPT BIOCHEM,MINNEAPOLIS,MN 55455
[2] UNIV MINNESOTA,SCH MED,INST HUMAN GENET,MINNEAPOLIS,MN 55455
关键词
D O I
10.2337/diabetes.43.4.546
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We observed in the HIT cell, a clonal insulin-secreting cell line, that epinephrine and somatostatin lower insulin mRNA levels and intracellular insulin content in addition to the well-recognized effect of these hormones to inhibit insulin secretion. To determine whether these inhibitory hormones might regulate insulin synthesis at the level of insulin gene transcription, we studied HIT cell expression of a human insulin-chloramphenicol acetyl transferase (CAT) reporter gene in the presence of glucose, epinephrine, and somatostatin. HIT cell expression of this human insulin-CAT reporter gene was responsive to glucose in a concentration-dependent manner, increasing threefold as the glucose concentration increased from 0.4 to 11 mM. Epinephrine significantly inhibited insulin-CAT reporter gene expression (61 +/- 5% of control), an effect mediated specifically by the human insulin gene promoter/enhancer sequence. Somatostatin significantly inhibited expression of the human insulin-CAT reporter gene (65 +/- 4% of control) and, to a lesser extent, expression of a control reporter gene, pRSVCAT (78 +/- 4% of control). Thus, somatostatin may inhibit insulin gene transcription by insulin gene-specific effects as well as more general effects on gene expression. Both epinephrine and somatostatin inhibited expression of the human insulin-CAT reporter gene in a concentration-dependent manner that paralleled inhibition of insulin secretion. These studies indicate that epinephrine and somatostatin lower HIT cell insulin mRNA levels in part by inhibiting insulin gene transcription. Thus, hormonal inhibition of insulin secretion may be coupled with inhibition of insulin synthesis, thereby allowing the beta-cell to match insulin supply to secretory demand.
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页码:546 / 551
页数:6
相关论文
共 32 条
[1]   NEUROPEPTIDERGIC VERSUS CHOLINERGIC AND ADRENERGIC REGULATION OF ISLET HORMONE-SECRETION [J].
AHREN, B ;
TABORSKY, GJ ;
PORTE, D .
DIABETOLOGIA, 1986, 29 (12) :827-836
[2]  
ALBERTI KGM, 1973, LANCET, V2, P1299
[3]  
BOAM DSW, 1990, J BIOL CHEM, V265, P8285
[4]   STUDIES ON MECHANISMS OF SOMATOSTATIN ACTION ON INSULIN RELEASE .4. EFFECT OF SOMATOSTATIN ON CYCLIC-AMP LEVELS AND PHOSPHODIESTERASE ACTIVITY IN ISOLATED RAT PANCREATIC-ISLETS [J].
CLARO, A ;
GRILL, V ;
EFENDIC, S ;
LUFT, R .
ACTA ENDOCRINOLOGICA, 1977, 85 (02) :379-388
[5]   REGULATION OF INSULIN SECRETION STUDIED WITH PIECES OF RABBIT PANCREAS INCUBATED IN VITRO [J].
COORE, HG ;
RANDLE, PJ .
BIOCHEMICAL JOURNAL, 1964, 93 (01) :66-&
[6]  
EFRAT S, 1991, J BIOL CHEM, V266, P11141
[7]   GALANIN INHIBITS PROINSULIN GENE-EXPRESSION STIMULATED BY THE INSULINOTROPIC HORMONE GLUCAGON-LIKE PEPTIDE-I(7-37) IN MOUSE INSULINOMA BETA-TC-1 CELLS [J].
FEHMANN, HC ;
HABENER, JF .
ENDOCRINOLOGY, 1992, 130 (05) :2890-2896
[8]   EFFECT OF 5'-FLANKING SEQUENCE DELETIONS ON EXPRESSION OF THE HUMAN INSULIN GENE IN TRANSGENIC MICE [J].
FROMONTRACINE, M ;
BUCCHINI, D ;
MADSEN, O ;
DESBOIS, P ;
LINDE, S ;
NIELSEN, JH ;
SAULNIER, C ;
RIPOCHE, MA ;
JAMI, J ;
PICTET, R .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (05) :669-677
[9]  
GERMAN MS, 1990, J BIOL CHEM, V265, P22063
[10]   CONTROL OF INSULIN GENE-EXPRESSION BY GLUCOSE [J].
GOODISON, S ;
KENNA, S ;
ASHCROFT, SJH .
BIOCHEMICAL JOURNAL, 1992, 285 :563-568