Ignet

Gene Information

Gene symbol: INHBE

Gene name: inhibin, beta E

HGNC ID: 24029

Synonyms: activin, MGC4638

Related Genes

#	Gene Symbol	Number of hits
1	ACVR1	1 hits
2	ACVR1B	1 hits
3	ACVR1C	1 hits
4	ACVR2A	1 hits
5	ACVR2B	1 hits
6	ACVRL1	1 hits
7	ADCYAP1	1 hits
8	ADIPOQ	1 hits
9	ALB	1 hits
10	ALPP	1 hits
11	ANGPT1	1 hits
12	BMP2	1 hits
13	BMP7	1 hits
14	BMPR1A	1 hits
15	BTC	1 hits
16	CGA	1 hits
17	COL1A1	1 hits
18	CRH	1 hits
19	CRHBP	1 hits
20	CRP	1 hits
21	CTSG	1 hits
22	CXCR4	1 hits
23	CYP19A1	1 hits
24	CYSLTR2	1 hits
25	DLL4	1 hits
26	ELN	1 hits
27	ENG	1 hits
28	EPHB2	1 hits
29	F11R	1 hits
30	FOXA2	1 hits
31	FSHB	1 hits
32	FST	1 hits
33	FSTL3	1 hits
34	GCG	1 hits
35	GNRH1	1 hits
36	GNRHR	1 hits
37	HBB	1 hits
38	HGF	1 hits
39	HHIP	1 hits
40	IL6	1 hits
41	INHBA	1 hits
42	INS	1 hits
43	KLRG1	1 hits
44	LEP	1 hits
45	LHB	1 hits
46	MAPK1	1 hits
47	MAPK14	1 hits
48	MAPK8	1 hits
49	MSTN	1 hits
50	NES	1 hits
51	NEUROD1	1 hits
52	NEUROG3	1 hits
53	NKX2-2	1 hits
54	PARD3	1 hits
55	PAX4	1 hits
56	PAX6	1 hits
57	PDX1	1 hits
58	PPY	1 hits
59	RAB13	1 hits
60	RAB3B	1 hits
61	RPSA	1 hits
62	RUNX2	1 hits
63	SMAD1	1 hits
64	SMAD2	1 hits
65	SMAD3	1 hits
66	SMAD4	1 hits
67	SOX17	1 hits
68	TCF7	1 hits
69	TCF7L2	1 hits
70	TDGF1	1 hits
71	TF	1 hits
72	TGFA	1 hits
73	TGFB1	1 hits
74	TGFB3	1 hits
75	TGFBR1	1 hits
76	VIP	1 hits
77	VLDLR	1 hits

Related Sentences

#	PMID	Sentence
1	1591345	Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats.
2	1671798	The effect of insulin and insulin-like growth factors were examined in closer detail because of the clinical association between insulin and hyperandrogenism.
3	1671798	Pituitary hormones and hypothalamic releasing factors, such as human ACTH (10 nM), beta-endorphin (10 nM), beta-lipotropin (10 nM), alpha-MSH (10 nM), gamma 3-MSH (10 nM), ovine luteinizing hormone (10 ng/ml), ovine follicle-stimulating hormone (10 ng/ml), ovine thyroid-stimulating hormone (10 ng/ml), rat growth hormone (10 ng/ml), rat prolactin (10 ng/ml), rat corticotropin-releasing factor (10 nM), luteinizing hormone-releasing factor (10 nM), thyrotropin-releasing factor (10 nM), human growth hormone-releasing factor (10 nM), and somatostatin (10 nM), have no significant effects on aromatase activity.
4	1671798	Porcine inhibin A (10 ng/ml) and porcine activin AB (10 ng/ml), two ovarian hormones with structural transforming homology to transforming growth factor-beta, also have no effect on aromatase activity.
5	1671798	Although basic fibroblast growth factor (1-100 ng/ml), acidic fibroblast growth factor (1 ng/ml), epidermal growth factor (1 ng/ml), platelet-derived growth factor (1 ng/ml), tumor necrosis factor (1 ng/ml), and transforming growth factor-beta 1 (1 ng/ml) have no effect on basal aromatase activity in human skin fibroblasts, all of these growth factors inhibited the ability of dibutyryladenosine 3',5'-cyclic monophosphate to stimulate aromatase activity.
6	1671798	In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM).
7	1671798	On the basis of the results presented here, it is interesting to speculate that the hyperandrogenism that is often associated with insulin resistance may be due to a combination of growth factor-mediated inhibition of aromatase activity and the failure of peripheral tissues to respond to insulin and metabolize androgens to estrogens.
8	1883364	Follistatin is a monomeric protein originally discovered in ovarian follicular fluid as a suppressor of pituitary follicle-stimulating hormone (FSH) secretion, and later identified as a binding protein for activin.
9	1883364	To explore the role of the Asn-linked carbohydrate chains on the follistatin molecule in regard to the inhibition of FSH secretion and activin binding ability, site-specific mutations were introduced at either or both of the two potential Asn-linked glycosylation sites of human follistatin with 315 amino acids (hFS-315).
10	1883364	When tested for their ability to inhibit FSH secretion and to bind activin, each mutant was found to have a similar property as the non-mutated recombinant hFS-315, suggesting that glycosylation of the follistatin molecule has no effect in these functions.
11	1883364	Follistatin is a monomeric protein originally discovered in ovarian follicular fluid as a suppressor of pituitary follicle-stimulating hormone (FSH) secretion, and later identified as a binding protein for activin.
12	1883364	To explore the role of the Asn-linked carbohydrate chains on the follistatin molecule in regard to the inhibition of FSH secretion and activin binding ability, site-specific mutations were introduced at either or both of the two potential Asn-linked glycosylation sites of human follistatin with 315 amino acids (hFS-315).
13	1883364	When tested for their ability to inhibit FSH secretion and to bind activin, each mutant was found to have a similar property as the non-mutated recombinant hFS-315, suggesting that glycosylation of the follistatin molecule has no effect in these functions.
14	1883364	Follistatin is a monomeric protein originally discovered in ovarian follicular fluid as a suppressor of pituitary follicle-stimulating hormone (FSH) secretion, and later identified as a binding protein for activin.
15	1883364	To explore the role of the Asn-linked carbohydrate chains on the follistatin molecule in regard to the inhibition of FSH secretion and activin binding ability, site-specific mutations were introduced at either or both of the two potential Asn-linked glycosylation sites of human follistatin with 315 amino acids (hFS-315).
16	1883364	When tested for their ability to inhibit FSH secretion and to bind activin, each mutant was found to have a similar property as the non-mutated recombinant hFS-315, suggesting that glycosylation of the follistatin molecule has no effect in these functions.
17	1909791	Follistatin and activin: a potential intrinsic regulatory system within diverse tissues.
18	2036994	Follistatin binds to both activin and inhibin through the common subunit.
19	2036994	Inhibin, activin, and follistatin are three families of polypeptides originally isolated and characterized from ovarian follicular fluid based on their modulation of FSH release from pituitary cell culture.
20	2036994	By contrast, the physiological significance of follistatin was obscure, until it was discovered that follistatin is a binding protein to activin.
21	2036994	Since activin binds to follistatin, it is imperative to determine the nature of the activin/follistatin binding complex.
22	2036994	Therefore, these results suggest that follistatin binds to both activin and inhibin through the common beta-subunit.
23	2036994	Follistatin binds to both activin and inhibin through the common subunit.
24	2036994	Inhibin, activin, and follistatin are three families of polypeptides originally isolated and characterized from ovarian follicular fluid based on their modulation of FSH release from pituitary cell culture.
25	2036994	By contrast, the physiological significance of follistatin was obscure, until it was discovered that follistatin is a binding protein to activin.
26	2036994	Since activin binds to follistatin, it is imperative to determine the nature of the activin/follistatin binding complex.
27	2036994	Therefore, these results suggest that follistatin binds to both activin and inhibin through the common beta-subunit.
28	2036994	Follistatin binds to both activin and inhibin through the common subunit.
29	2036994	Inhibin, activin, and follistatin are three families of polypeptides originally isolated and characterized from ovarian follicular fluid based on their modulation of FSH release from pituitary cell culture.
30	2036994	By contrast, the physiological significance of follistatin was obscure, until it was discovered that follistatin is a binding protein to activin.
31	2036994	Since activin binds to follistatin, it is imperative to determine the nature of the activin/follistatin binding complex.
32	2036994	Therefore, these results suggest that follistatin binds to both activin and inhibin through the common beta-subunit.
33	2036994	Follistatin binds to both activin and inhibin through the common subunit.
34	2036994	Inhibin, activin, and follistatin are three families of polypeptides originally isolated and characterized from ovarian follicular fluid based on their modulation of FSH release from pituitary cell culture.
35	2036994	By contrast, the physiological significance of follistatin was obscure, until it was discovered that follistatin is a binding protein to activin.
36	2036994	Since activin binds to follistatin, it is imperative to determine the nature of the activin/follistatin binding complex.
37	2036994	Therefore, these results suggest that follistatin binds to both activin and inhibin through the common beta-subunit.
38	2036994	Follistatin binds to both activin and inhibin through the common subunit.
39	2036994	Inhibin, activin, and follistatin are three families of polypeptides originally isolated and characterized from ovarian follicular fluid based on their modulation of FSH release from pituitary cell culture.
40	2036994	By contrast, the physiological significance of follistatin was obscure, until it was discovered that follistatin is a binding protein to activin.
41	2036994	Since activin binds to follistatin, it is imperative to determine the nature of the activin/follistatin binding complex.
42	2036994	Therefore, these results suggest that follistatin binds to both activin and inhibin through the common beta-subunit.
43	2121404	The closed-loop feedback mechanism of ovarian inhibin and pituitary FSH has been joined by possible "inhibin-like" actions of follistatin and FSH-stimulatory effects of activin.
44	2121404	Figure 3 shows a simplistic diagram summarizing our current understanding of inhibin/activin and follistatin action along the hypothalamic-pituitary-gonadal axis.
45	2121404	The closed-loop feedback mechanism of ovarian inhibin and pituitary FSH has been joined by possible "inhibin-like" actions of follistatin and FSH-stimulatory effects of activin.
46	2121404	Figure 3 shows a simplistic diagram summarizing our current understanding of inhibin/activin and follistatin action along the hypothalamic-pituitary-gonadal axis.
47	7887917	The heparin binding site of follistatin is involved in its interaction with activin.
48	7887917	Whether the heparin-binding site of follistatin would interact with activin has been examined.
49	7887917	This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin.
50	7887917	These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315.
51	7887917	These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin.
52	7887917	The heparin binding site of follistatin is involved in its interaction with activin.
53	7887917	Whether the heparin-binding site of follistatin would interact with activin has been examined.
54	7887917	This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin.
55	7887917	These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315.
56	7887917	These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin.
57	7887917	The heparin binding site of follistatin is involved in its interaction with activin.
58	7887917	Whether the heparin-binding site of follistatin would interact with activin has been examined.
59	7887917	This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin.
60	7887917	These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315.
61	7887917	These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin.
62	7887917	The heparin binding site of follistatin is involved in its interaction with activin.
63	7887917	Whether the heparin-binding site of follistatin would interact with activin has been examined.
64	7887917	This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin.
65	7887917	These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315.
66	7887917	These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin.
67	7887917	The heparin binding site of follistatin is involved in its interaction with activin.
68	7887917	Whether the heparin-binding site of follistatin would interact with activin has been examined.
69	7887917	This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin.
70	7887917	These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315.
71	7887917	These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin.
72	8333840	Differential control of activin, inhibin and follistatin proteins in cultured rat granulosa cells.
73	8333840	Follistatin, activin and inhibin proteins are produced by granulosa cells, but the mechanisms controlling their production remain unclear.
74	8333840	Here, we examined how the protein kinase A (PKA) and protein kinase C (PKC) pathways act and interact to regulate production of these proteins.
75	8333840	Conditioned media were assayed for inhibin and activin by ligand blotting using recombinant human 125I-follistatin and for follistatin by double ligand blotting using cold activin plus 125I-follistatin.
76	8333840	In contrast, GnRH and TPA stimulated activin, and to a lesser degree, inhibin production; significantly, this is the first demonstration of activin dimer production by granulosa cells.
77	8333840	Differential control of activin, inhibin and follistatin proteins in cultured rat granulosa cells.
78	8333840	Follistatin, activin and inhibin proteins are produced by granulosa cells, but the mechanisms controlling their production remain unclear.
79	8333840	Here, we examined how the protein kinase A (PKA) and protein kinase C (PKC) pathways act and interact to regulate production of these proteins.
80	8333840	Conditioned media were assayed for inhibin and activin by ligand blotting using recombinant human 125I-follistatin and for follistatin by double ligand blotting using cold activin plus 125I-follistatin.
81	8333840	In contrast, GnRH and TPA stimulated activin, and to a lesser degree, inhibin production; significantly, this is the first demonstration of activin dimer production by granulosa cells.
82	8333840	Differential control of activin, inhibin and follistatin proteins in cultured rat granulosa cells.
83	8333840	Follistatin, activin and inhibin proteins are produced by granulosa cells, but the mechanisms controlling their production remain unclear.
84	8333840	Here, we examined how the protein kinase A (PKA) and protein kinase C (PKC) pathways act and interact to regulate production of these proteins.
85	8333840	Conditioned media were assayed for inhibin and activin by ligand blotting using recombinant human 125I-follistatin and for follistatin by double ligand blotting using cold activin plus 125I-follistatin.
86	8333840	In contrast, GnRH and TPA stimulated activin, and to a lesser degree, inhibin production; significantly, this is the first demonstration of activin dimer production by granulosa cells.
87	8333840	Differential control of activin, inhibin and follistatin proteins in cultured rat granulosa cells.
88	8333840	Follistatin, activin and inhibin proteins are produced by granulosa cells, but the mechanisms controlling their production remain unclear.
89	8333840	Here, we examined how the protein kinase A (PKA) and protein kinase C (PKC) pathways act and interact to regulate production of these proteins.
90	8333840	Conditioned media were assayed for inhibin and activin by ligand blotting using recombinant human 125I-follistatin and for follistatin by double ligand blotting using cold activin plus 125I-follistatin.
91	8333840	In contrast, GnRH and TPA stimulated activin, and to a lesser degree, inhibin production; significantly, this is the first demonstration of activin dimer production by granulosa cells.
92	8462476	Follistatin, a monomeric protein originally isolated from ovarian follicular fluid, is now believed to be a major local regulator of the multifaceted actions of activin by virtue of its activin-binding properties.
93	8472873	Structural and functional characterization of the rat follistatin (activin-binding protein) gene promoter.
94	8472873	Follistatin was originally identified as a specific inhibitor of follicle stimulating hormone secretion and later characterized as a binding protein for activin.
95	8472873	Since activin regulates hormone secretion and cell differentiation, the importance of understanding the mechanisms regulating the synthesis of its binding protein, follistatin, is evident.
96	8472873	Co-treatment with forskolin and TPA resulted in a 6.4-fold induction in its promoter activity, suggesting that two distinct signal transduction pathways, the cAMP-dependent protein kinase-A pathway and diacylglycerol-dependent protein kinase-C pathway, act coordinately to modulate follistatin gene transcription.
97	8472873	Structural and functional characterization of the rat follistatin (activin-binding protein) gene promoter.
98	8472873	Follistatin was originally identified as a specific inhibitor of follicle stimulating hormone secretion and later characterized as a binding protein for activin.
99	8472873	Since activin regulates hormone secretion and cell differentiation, the importance of understanding the mechanisms regulating the synthesis of its binding protein, follistatin, is evident.
100	8472873	Co-treatment with forskolin and TPA resulted in a 6.4-fold induction in its promoter activity, suggesting that two distinct signal transduction pathways, the cAMP-dependent protein kinase-A pathway and diacylglycerol-dependent protein kinase-C pathway, act coordinately to modulate follistatin gene transcription.
101	8472873	Structural and functional characterization of the rat follistatin (activin-binding protein) gene promoter.
102	8472873	Follistatin was originally identified as a specific inhibitor of follicle stimulating hormone secretion and later characterized as a binding protein for activin.
103	8472873	Since activin regulates hormone secretion and cell differentiation, the importance of understanding the mechanisms regulating the synthesis of its binding protein, follistatin, is evident.
104	8472873	Co-treatment with forskolin and TPA resulted in a 6.4-fold induction in its promoter activity, suggesting that two distinct signal transduction pathways, the cAMP-dependent protein kinase-A pathway and diacylglycerol-dependent protein kinase-C pathway, act coordinately to modulate follistatin gene transcription.
105	8477666	Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.
106	8477666	For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin.
107	8477666	Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats.
108	8477666	Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin.
109	8477666	Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.
110	8477666	Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.
111	8477666	For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin.
112	8477666	Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats.
113	8477666	Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin.
114	8477666	Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.
115	8477666	Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.
116	8477666	For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin.
117	8477666	Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats.
118	8477666	Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin.
119	8477666	Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.
120	8477666	Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.
121	8477666	For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin.
122	8477666	Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats.
123	8477666	Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin.
124	8477666	Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.
125	8477666	Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.
126	8477666	For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin.
127	8477666	Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats.
128	8477666	Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin.
129	8477666	Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.
130	8890726	Mean +/- SEM values of serum activin A were significantly higher in patients with preterm labor and gestational diabetes than in controls (p < 0.01), showing a significant decrease following insulin therapy in diabetic patients (p < 0.01).
131	9436357	The TGF-beta family, the activin family, and bone morphogenic proteins belong to the TGF-beta superfamily.
132	9436357	Smad family members (Smad 1, Smad 2, Smad 3 and Smad 4) are expressed in the cultured retinal pigmant epithelial cell line (D407), in which TGF-beta and activin A stimulate the translocation of Smad 2, but not Smad 1 into nuclei, whereas bone morphogenetic protein (BMP) stimulates that of Smad 1, but not Smad 2.
133	9436357	The TGF-beta family, the activin family, and bone morphogenic proteins belong to the TGF-beta superfamily.
134	9436357	Smad family members (Smad 1, Smad 2, Smad 3 and Smad 4) are expressed in the cultured retinal pigmant epithelial cell line (D407), in which TGF-beta and activin A stimulate the translocation of Smad 2, but not Smad 1 into nuclei, whereas bone morphogenetic protein (BMP) stimulates that of Smad 1, but not Smad 2.
135	9524732	Regulation of pulsatile secretion of growth hormone (GH) relies on hypothalamic neuronal loops, major transmitters involved in their operation are growth hormone releasing hormone (GHRH) synthetized mostly in arcuate nucleus (ARC) neurons, and somatostatin (SRIH), synthetized both in hypothalamus periventricular (PVe) and ARC neurons. 2.
136	9524732	Other neuropeptides synthetized in ARC neurons, such as galanin, or in ARC interneurons, such as neuropeptide Y (NPY), are able to modulate synthesis and release of GHRH and SRIH into the hypothalamohypophyseal portal system. 3.
137	9524732	At the pituitary level, major neurotransmitters regulating GH cells act on receptors of the VIP/PACAP/GHRH family and of the somatostatin family, in particular, sst2 and sst3.
138	9524732	Regulation and differentiation of somatotropes also depend upon paracrine processes within the pituitary itself and involve growth factors and several neuropeptides, for instance, vasoactive intestinal peptide, angiotensin 2, endothelin, and activin. 10.
139	10102170	Based on data from patients with established disease, with the involvement of various organ systems, potential candidate markers would include renal function (kallikrein-creatinine); coagulation and fibrinolytic systems and platelet activation (platelet volume); markers of vascular function (fibronectin, prostacyclin, thromboxane) and oxidant stress (lipid peroxides, 8-isoprostane, antioxidants, anticardiolipin antibodies, hemoglobin, iron, transferrin, homocysteine, hypertriglyceridemia, albumin isoforms); placental peptide hormones (CRH, CRHbp, activin, inhibin, hCG); vascular resistance (uteroplacental flow velocity waveforms); genetic markers; insulin resistance; and glucose intolerance.
140	10334306	Dexamethasone (Dx) converts them to exocrine cells, whereas activin A (Act) converts them into endocrine cells expressing pancreatic polypeptide.
141	10334306	A combination of Act and betacellulin (BTC) converts them further into insulin-secreting cells.
142	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
143	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
144	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
145	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
146	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
147	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
148	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
149	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
150	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
151	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
152	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
153	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
154	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
155	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
156	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
157	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
158	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
159	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
160	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
161	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
162	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
163	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
164	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
165	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
166	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
167	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
168	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
169	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
170	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
171	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
172	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
173	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
174	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
175	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
176	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
177	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
178	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
179	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
180	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
181	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
182	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
183	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
184	10853708	Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age.
185	10853708	The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets.
186	10853708	In absence of glucose, activin A did not modify insulin secretion at the different concentrations used.
187	10853708	In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern.
188	10853708	In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM).
189	10853708	Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001).
190	10853708	The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.
191	11249068	PDX-1 plays a critical role in pancreatic development and insulin secretion.
192	11249068	The ARIP and ARIP/PDX-1 cells were treated with known growth and differentiation factors including hepatocyte growth factor, activin A, betacellulin, reg, INGAP, nicotinamide, and retinoic acid.
193	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
194	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
195	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
196	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
197	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
198	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
199	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
200	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
201	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
202	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
203	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
204	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
205	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
206	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
207	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
208	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
209	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
210	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
211	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
212	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
213	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
214	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
215	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
216	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
217	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
218	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
219	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
220	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
221	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
222	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
223	11272164	Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF).
224	11272164	These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF.
225	11272164	Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF.
226	11272164	In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A.
227	11272164	Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF.
228	11272164	These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
229	11334431	No evidence for linkage or for diabetes-associated mutations in the activin type 2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the young or type 2 diabetes.
230	11334431	For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B).
231	11334431	No evidence for linkage or for diabetes-associated mutations in the activin type 2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the young or type 2 diabetes.
232	11334431	For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B).
233	11675415	Bone morphogenetic protein-7 (BMP7), a member of the transforming growth factor-beta (TGF-beta) superfamily of cytokines, is highly expressed in renal tubules and generally promotes maintenance of epithelial phenotype.
234	11675415	Renal expression of the high-affinity BMP type II receptor and the type I receptor Alk2 (activin receptor-like kinase-2) decreased.
235	11675415	Alk3 tended to decrease, but Alk6 remained unchanged.
236	11675415	In cultured tubular cells, TGF-beta reduced BMP7 and Alk3 expression and increased gremlin but did not interrupt BMP7-induced activation of smad5 or Erk1 and -2.
237	11675415	In contrast, BMP7 did not alter TGF-beta expression.
238	11675415	Neutralization of endogenous BMP7 in cultured proximal tubular cells raised the expression of fibronectin and tended to increase collagen alpha(1) III mRNA levels.
239	11675415	In conclusion, in experimental diabetic nephropathy, renal tubular BMP7 and some of its receptors decreased and gremlin, a secreted BMP antagonist, increased.
240	12114736	We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion.
241	12114736	In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats.
242	12114736	No rh activin AIEDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PR) cells in the islets, or in the exocrine cells.
243	12114736	The in situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells.
244	12114736	These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.
245	12114736	We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion.
246	12114736	In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats.
247	12114736	No rh activin AIEDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PR) cells in the islets, or in the exocrine cells.
248	12114736	The in situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells.
249	12114736	These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.
250	12114736	We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion.
251	12114736	In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats.
252	12114736	No rh activin AIEDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PR) cells in the islets, or in the exocrine cells.
253	12114736	The in situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells.
254	12114736	These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.
255	12114736	We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion.
256	12114736	In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats.
257	12114736	No rh activin AIEDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PR) cells in the islets, or in the exocrine cells.
258	12114736	The in situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells.
259	12114736	These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.
260	12114736	We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion.
261	12114736	In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats.
262	12114736	No rh activin AIEDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PR) cells in the islets, or in the exocrine cells.
263	12114736	The in situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells.
264	12114736	These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.
265	12606518	Following treatment of AR42J cells with activin A and hepatocyte growth factor, the protein levels of h1-calponin decreased in a time-dependent manner during the course of the cell differentiation.
266	14514635	Nestin was visualized in the platelet endothelial cell adhesion molecule and alpha smooth muscle actin-positive blood vessels and colocalized with vimentin in the interstitium.
267	14514635	Nestin was not observed in pan cytokeratin (pCK)-positive ductal epithelium or insulin cells.
268	14514635	Purified nestin+ cells also coexpressed vimentin and lacked pCK immunoreactivity.
269	14514635	Exposure of selected nestin+ cells to nicotinamide, hepatocyte growth factor/scatter factor, betacellulin, activin A, or exendin-4 failed to induce pancreatic and duodenal homeobox gene-1 or insulin message as determined by RT-PCR.
270	14514635	Transplantation of nestin+ cells and fetal pancreatic fibroblasts into athymic mice also failed to result in the development of beta-cells, whereas nestin- fetal pancreatic epithelial cells gave rise to functional insulin-secreting beta-cells.
271	14732718	Type IV collagen is transcriptionally regulated by Smad1 under advanced glycation end product (AGE) stimulation.
272	14732718	To elucidate the interaction between transforming growth factor-beta and Smad1, we investigated whether activin receptor-liked kinase1 (ALK1) was involved in this regulation.
273	14732718	We also demonstrated that Smad1 and ALK1 were highly expressed in human diabetic nephropathy.
274	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
275	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
276	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
277	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
278	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
279	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
280	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
281	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
282	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
283	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
284	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
285	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
286	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
287	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
288	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
289	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
290	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
291	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
292	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
293	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
294	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
295	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
296	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
297	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
298	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
299	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
300	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
301	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
302	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
303	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
304	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
305	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
306	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
307	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
308	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
309	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
310	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
311	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
312	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
313	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
314	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
315	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
316	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
317	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
318	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
319	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
320	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
321	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
322	14988244	In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells.
323	14988244	One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC.
324	14988244	Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading.
325	14988244	The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months.
326	14988244	Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells.
327	14988244	The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC.
328	14988244	In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased.
329	14988244	These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
330	15154911	The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF-beta/activin, shows that most of the pro-fibrotic activities of TGF-beta are mediated by Smad3.
331	15154911	Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF-beta and do not autoinduce TGF-beta.
332	15154911	The loss of Smad3 also interferes with TGF-beta-mediated induction of EMT and genes for collagens, plasminogen activator inhibitor-1 and the tissue inhibitor of metalloprotease-1.
333	15154911	Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation-induced fibrosis.
334	15180456	Activins, myostatin and related TGF-beta family members as novel therapeutic targets for endocrine, metabolic and immune disorders.
335	15180456	Recent studies have revealed that activins and myostatin signal through activin type II receptors (ActRIIA and ActRIIB) and their activities are regulated by extracellular binding proteins, follistatins and follistatin-related gene (FLRG).
336	15232060	The FSH-beta and GnRH-receptor genes are up-regulated by pituitary activin and down-regulated by pituitary follistatin, and circulating inhibin disrupts this local regulation by functioning as an endogenous competitor of the activin receptor.
337	15232060	There is evidence that the intra-pituitary regulation of FSH-beta and GnRH-receptor gene expression may activate pubertal maturation in male rats.
338	15277382	Interestingly, the expression of endogenous cellular inhibitors of activin signaling, follistatin and Cripto, were also found to be augmented.
339	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
340	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
341	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
342	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
343	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
344	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
345	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
346	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
347	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
348	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
349	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
350	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
351	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
352	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
353	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
354	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
355	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
356	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
357	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
358	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
359	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
360	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
361	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
362	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
363	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
364	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
365	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
366	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
367	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
368	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
369	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
370	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
371	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
372	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
373	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
374	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
375	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
376	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
377	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
378	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
379	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
380	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
381	15319828	Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH).
382	15319828	Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism.
383	15319828	Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH.
384	15319828	Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion.
385	15319828	Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways.
386	15319828	This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins.
387	15319828	The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter.
388	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
389	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
390	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
391	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
392	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
393	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
394	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
395	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
396	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
397	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
398	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
399	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
400	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
401	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
402	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
403	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
404	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
405	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
406	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
407	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
408	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
409	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
410	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
411	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
412	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
413	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
414	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
415	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
416	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
417	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
418	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
419	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
420	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
421	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
422	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
423	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
424	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
425	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
426	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
427	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
428	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
429	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
430	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
431	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
432	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
433	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
434	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
435	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
436	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
437	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
438	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
439	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
440	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
441	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
442	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
443	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
444	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
445	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
446	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
447	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
448	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
449	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
450	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
451	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
452	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
453	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
454	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
455	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
456	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
457	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
458	15375186	Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene.
459	15375186	Both activin and GnRH can independently stimulate expression of the FSHbeta subunit gene.
460	15375186	In this study, we used the gonadotrope-derived LbetaT2 cell line to investigate the potential interaction between activin and GnRH in regulating the transcriptional activity of the rat FSHbeta gene promoter.
461	15375186	Activin A and GnRH synergistically enhanced rat FSHbeta transcriptional activity.
462	15375186	Overexpression of SMAD3 (mediator of decapentaplegic-related protein 3), but not of SMAD2, increased transcriptional activation of the rat (r) FSHbeta gene promoter, which was further enhanced by the combined overexpression of SMAD3 and 4 (3+4).
463	15375186	The stimulatory effects of SMAD3 overexpression were localized to -472/-256 of the rFSHbeta gene promoter, and activin- and GnRH-responsive proteins were shown to bind to region -284/-252.
464	15375186	Mutation of two bases located in the center of this palindrome effectively abrogated SMAD4 binding, markedly reduced SMAD3 and 3+4 stimulation of the rFSHbeta gene promoter, and significantly decreased the synergistic enhancement of promoter activity by both activin A and GnRH, and SMAD3 and GnRH.
465	15375186	Blockade of the MAPK-signaling pathway did not significantly affect the response to combined stimulation with activin and GnRH.
466	15375186	In contrast, interference with SMAD3 signaling caused a significant reduction in activin and GnRH synergy.
467	15375186	The results indicate that SMAD3 plays an important role in the synergistic effects of activin and GnRH and demonstrate that this synergy is mediated by a palindromic cis-element located at -266/-259 of the rFSHbeta gene promoter.
468	15504962	Interplay of glucagon-like peptide-1 and transforming growth factor-beta signaling in insulin-positive differentiation of AR42J cells.
469	15504962	Exogenous activin, possibly working through intracellular smad 2 and/or smad 3, as well as exogenous exendin-4 (a long-acting glucagon-like peptide-1 agonist) have both been shown to induce insulin-positive/endocrine differentiation in AR42J cells.
470	15504962	In particular, insulin-positive differentiation seems to entail an exendin-4-induced drop in smad 2 and elevation in smad 3 in RNA levels.
471	15504962	The coapplication of exogenous exendin-4 and, specifically, low-dose exogenous TGF-beta1 led to a dramatic 20-fold increase in insulin mRNA levels, supporting a novel synergistic and codependent relationship between exendin-4 signaling and TGF-beta isoform signaling.
472	15849173	Here we show that a simple three-step experimental approach based on the combination induction by activin A, all-trans retinoic acid, and other mature factors is able to induce murine ESCs to differentiate into insulin-producing cells in 2 weeks, and that insulin release of these induced cells is regulated by the glucose concentration.
473	16020542	Cross-talk between bone morphogenetic protein and transforming growth factor-beta signaling is essential for exendin-4-induced insulin-positive differentiation of AR42J cells.
474	16020542	We found that the canonical intracellular mediators of BMP signaling, Smad-1 and Smad-8, were significantly elevated in AR42J cells undergoing insulin-positive differentiation in response to exendin-4 treatment, suggesting a role for BMP signaling in beta-cell formation.
475	16020542	Similarly, endogenous BMP-2 ligand and ALK-1 receptor (activin receptor-like kinase-1; known to activate Smads 1 and 8) mRNAs were specifically up-regulated in exendin-4-treated AR42J cells.
476	16020542	Surprisingly, Smad-1 and Smad-8 levels were suppressed by the addition of BMP-soluble receptor inhibition of BMP ligand binding to its receptor.
477	16020542	BMP-2 ligand antisense also strongly inhibited Smad-1 and Smad-8 expression, again with the abolition of insulin-positive differentiation.
478	16020542	In short, BMP signaling may represent a novel downstream target of exendin-4 (glucagon-like peptide 1) signaling and potentially serve as an upstream regulator of transforming growth factor-beta isoform signaling to differentiate the acinar-like AR42J cells into insulin-secreting cells.
479	16123344	We have previously demonstrated that the expression of the beta-cell transcription factor pancreatic duodenal homeobox 1 (PDX-1) in human fetal liver cells activates multiple aspects of the beta-cell phenotype.
480	16123344	Cells cultured with activin A in serum-free medium upregulated expression of NeuroD and Nkx2.2 and downregulated paired box homeotic gene 6 (PAX-6).
481	16123344	Glucokinase and prohormone convertase 1/3 were also upregulated, whereas pancreatic polypeptide and glucagon as well as liver markers were downregulated.
482	16934249	Furthermore, pGL3.hINS-363 3x shows significant promoter activity in differentiated AR42J cells that can produce insulin after activin A and betacellulin treatment.
483	17229845	FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults.
484	17229845	Activin and myostatin are related members of the TGF-beta growth factor superfamily.
485	17229845	FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist whose physiological role in adults remains to be determined.
486	17229845	We found that homozygous FSTL3 knockout adults developed a distinct group of metabolic phenotypes, including increased pancreatic islet number and size, beta cell hyperplasia, decreased visceral fat mass, improved glucose tolerance, and enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant patients.
487	17229845	This combination of phenotypes appears to arise from increased activin and myostatin bioactivity in specific tissues resulting from the absence of the FSTL3 antagonist.
488	17229845	Reduced visceral fat is consistent with a role for increased myostatin action in regulating fat deposition, which, in turn, may be partly responsible for the enhanced glucose tolerance and insulin sensitivity.
489	17229845	Our results demonstrate that FSTL3 regulation of activin and myostatin is critical for normal adult metabolic homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might simultaneously reduce visceral adiposity, increase beta cell mass, and improve insulin sensitivity.
490	17229845	FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults.
491	17229845	Activin and myostatin are related members of the TGF-beta growth factor superfamily.
492	17229845	FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist whose physiological role in adults remains to be determined.
493	17229845	We found that homozygous FSTL3 knockout adults developed a distinct group of metabolic phenotypes, including increased pancreatic islet number and size, beta cell hyperplasia, decreased visceral fat mass, improved glucose tolerance, and enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant patients.
494	17229845	This combination of phenotypes appears to arise from increased activin and myostatin bioactivity in specific tissues resulting from the absence of the FSTL3 antagonist.
495	17229845	Reduced visceral fat is consistent with a role for increased myostatin action in regulating fat deposition, which, in turn, may be partly responsible for the enhanced glucose tolerance and insulin sensitivity.
496	17229845	Our results demonstrate that FSTL3 regulation of activin and myostatin is critical for normal adult metabolic homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might simultaneously reduce visceral adiposity, increase beta cell mass, and improve insulin sensitivity.
497	17229845	FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults.
498	17229845	Activin and myostatin are related members of the TGF-beta growth factor superfamily.
499	17229845	FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist whose physiological role in adults remains to be determined.
500	17229845	We found that homozygous FSTL3 knockout adults developed a distinct group of metabolic phenotypes, including increased pancreatic islet number and size, beta cell hyperplasia, decreased visceral fat mass, improved glucose tolerance, and enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant patients.
501	17229845	This combination of phenotypes appears to arise from increased activin and myostatin bioactivity in specific tissues resulting from the absence of the FSTL3 antagonist.
502	17229845	Reduced visceral fat is consistent with a role for increased myostatin action in regulating fat deposition, which, in turn, may be partly responsible for the enhanced glucose tolerance and insulin sensitivity.
503	17229845	Our results demonstrate that FSTL3 regulation of activin and myostatin is critical for normal adult metabolic homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might simultaneously reduce visceral adiposity, increase beta cell mass, and improve insulin sensitivity.
504	17267584	Pioglitazone induces apoptosis in human vascular smooth muscle cells from diabetic patients involving the transforming growth factor-beta/activin receptor-like kinase-4/5/7/Smad2 signaling pathway.
505	17267584	Here, we aimed to study whether pioglitazone was able to induce apoptosis in VSMC from diabetic patients (DP) and, if so, whether the transforming growth factor (TGF)-beta1/Smad-2 pathway was involved.
506	17267584	This apoptotic effect was inhibited by the activin receptor-like kinase-4/5/7/Smad2 inhibitor 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide (SB-431542), denoting that the TGF-beta1/Smad-2 pathway was involved.
507	17267584	Pioglitazone rapidly increased the extracellular TGF-beta1 levels and concomitantly induced phosphorylation of Smad2 in VSMC from DP and NDP.
508	17267584	Pioglitazone induces apoptosis in human vascular smooth muscle cells from diabetic patients involving the transforming growth factor-beta/activin receptor-like kinase-4/5/7/Smad2 signaling pathway.
509	17267584	Here, we aimed to study whether pioglitazone was able to induce apoptosis in VSMC from diabetic patients (DP) and, if so, whether the transforming growth factor (TGF)-beta1/Smad-2 pathway was involved.
510	17267584	This apoptotic effect was inhibited by the activin receptor-like kinase-4/5/7/Smad2 inhibitor 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide (SB-431542), denoting that the TGF-beta1/Smad-2 pathway was involved.
511	17267584	Pioglitazone rapidly increased the extracellular TGF-beta1 levels and concomitantly induced phosphorylation of Smad2 in VSMC from DP and NDP.
512	17272496	Concomitantly, downregulation of the pancreas marker Pdx1 was recorded in activin-treated EBs, a phenomenon that was prevented by antagonizing Hedgehog signaling with Hedgehog interacting protein.
513	17303930	Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells.
514	17303930	Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively.
515	17303930	We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation.
516	17303930	In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells.
517	17303930	Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation.
518	17303930	Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin.
519	17303930	Furthermore, cells treated with conophylline and betacellulin-delta4 secreted insulin in response to glucose.
520	17303930	Likewise, conophylline and betacellulin-delta4 converted pancreatic ductal cells into insulin-producing cells.
521	17303930	Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin.
522	17303930	Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice.
523	17303930	Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.
524	17303930	Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells.
525	17303930	Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively.
526	17303930	We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation.
527	17303930	In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells.
528	17303930	Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation.
529	17303930	Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin.
530	17303930	Furthermore, cells treated with conophylline and betacellulin-delta4 secreted insulin in response to glucose.
531	17303930	Likewise, conophylline and betacellulin-delta4 converted pancreatic ductal cells into insulin-producing cells.
532	17303930	Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin.
533	17303930	Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice.
534	17303930	Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.
535	17303930	Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells.
536	17303930	Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively.
537	17303930	We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation.
538	17303930	In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells.
539	17303930	Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation.
540	17303930	Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin.
541	17303930	Furthermore, cells treated with conophylline and betacellulin-delta4 secreted insulin in response to glucose.
542	17303930	Likewise, conophylline and betacellulin-delta4 converted pancreatic ductal cells into insulin-producing cells.
543	17303930	Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin.
544	17303930	Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice.
545	17303930	Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.
546	17510217	In this 36-day protocol, hESCs were treated with sodium butyrate and activin A to generate definitive endoderm coexpressing CXCR4 and Sox17, and CXCR4 and Foxa2.
547	17510217	The endoderm population was then converted into cellular aggregates and further differentiated to Pdx1-expressing pancreatic endoderm in the presence of epidermal growth factor, basic fibroblast growth factor, and noggin.
548	17510217	The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide.
549	17652186	Inhibin and activin are members of the TGFbeta family that perform mutually antagonistic signaling roles in the anterior pituitary, gonads, and adrenal gland.
550	17652186	In this study, we demonstrate that Smad3, a key effector of activin signaling, is expressed at high levels and is constitutively activated in tumors from these mice.
551	17652186	The decrease in cyclinD2 levels in compound knockout mice is related to a reduction in mitogenic signaling through the phosphoinositide-3-kinase (PI3-kinase)/Akt pathway, which is required for normal cell cycle progression in tumor cells.
552	17652186	Loss of PI3-kinase/Akt signaling cannot be attributed to alterations in IGF expression, suggesting instead that signaling through the FSH receptor is attenuated.
553	17652186	Gene expression profiling in the ovaries of Madh3-/- and Inha-/-:Madh3-/- compound knockout mice supports this hypothesis and further suggests that Smad3 is specifically required for FSH to activate PI3-kinase/Akt, but not protein kinase A.
554	17652186	Together these observations imply that activin/Smad3 signaling is necessary for efficient signaling by FSH in Inha-/- tumor cells and that interruption of this pathway uncouples FSH from its intracellular mitogenic effectors.
555	17652186	Inhibin and activin are members of the TGFbeta family that perform mutually antagonistic signaling roles in the anterior pituitary, gonads, and adrenal gland.
556	17652186	In this study, we demonstrate that Smad3, a key effector of activin signaling, is expressed at high levels and is constitutively activated in tumors from these mice.
557	17652186	The decrease in cyclinD2 levels in compound knockout mice is related to a reduction in mitogenic signaling through the phosphoinositide-3-kinase (PI3-kinase)/Akt pathway, which is required for normal cell cycle progression in tumor cells.
558	17652186	Loss of PI3-kinase/Akt signaling cannot be attributed to alterations in IGF expression, suggesting instead that signaling through the FSH receptor is attenuated.
559	17652186	Gene expression profiling in the ovaries of Madh3-/- and Inha-/-:Madh3-/- compound knockout mice supports this hypothesis and further suggests that Smad3 is specifically required for FSH to activate PI3-kinase/Akt, but not protein kinase A.
560	17652186	Together these observations imply that activin/Smad3 signaling is necessary for efficient signaling by FSH in Inha-/- tumor cells and that interruption of this pathway uncouples FSH from its intracellular mitogenic effectors.
561	17652186	Inhibin and activin are members of the TGFbeta family that perform mutually antagonistic signaling roles in the anterior pituitary, gonads, and adrenal gland.
562	17652186	In this study, we demonstrate that Smad3, a key effector of activin signaling, is expressed at high levels and is constitutively activated in tumors from these mice.
563	17652186	The decrease in cyclinD2 levels in compound knockout mice is related to a reduction in mitogenic signaling through the phosphoinositide-3-kinase (PI3-kinase)/Akt pathway, which is required for normal cell cycle progression in tumor cells.
564	17652186	Loss of PI3-kinase/Akt signaling cannot be attributed to alterations in IGF expression, suggesting instead that signaling through the FSH receptor is attenuated.
565	17652186	Gene expression profiling in the ovaries of Madh3-/- and Inha-/-:Madh3-/- compound knockout mice supports this hypothesis and further suggests that Smad3 is specifically required for FSH to activate PI3-kinase/Akt, but not protein kinase A.
566	17652186	Together these observations imply that activin/Smad3 signaling is necessary for efficient signaling by FSH in Inha-/- tumor cells and that interruption of this pathway uncouples FSH from its intracellular mitogenic effectors.
567	17710734	Folliculostellate cells are targets of cytokines, peptides, and steroid hormones, and produce growth factors and cytokines, including follistatin, the dynamic regulator of follicle-stimulating hormone (FSH) production that binds activin, and limits activin signaling.
568	17710734	Pituitary adenylate cyclase-activating peptide (PACAP) and its receptor are found in folliculostellate cells in which they stimulate transcription of the follistatin gene through cyclic adenosine monophosphate/protein kinase A (PKA) signaling.
569	17710734	When PACAP increases, follistatin levels increase, and FSH-beta mRNA is reduced.
570	17710734	PACAP also activates gonadotrophs to stimulate transcription of the gonadotropin alpha-subunit gene and lengthen the LH-beta mRNA, presumably to prolong it half-life, and increases responsiveness to GnRH.
571	17989064	In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels.
572	17989064	Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets.
573	17989064	Treatment of islets with 5-Aza-2'-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression.
574	18023369	Differential effect of activin on mouse embryonic stem cell differentiation in insulin-secreting cells under nestin-positive selection and spontaneous differentiation protocols.
575	18023369	To increase the efficiency of endocrine pancreatic-like cell differentiation from mouse embryonic stem cells (ESCs), we applied activin-B to nestin-positive selection (protocol 1) and spontaneous differentiation (protocol 2) in different groups including: [A] activin-B, or [B] basic fibroblast growth factor (bFGF), and/or [C] activin-B+bFGF.
576	18023369	In conclusion, Addition of activin-B in a nestin-positive selection protocol increased the insulin-secreting cells in comparison with the same protocol with bFGF and/or spontaneous differentiation in presence of bFGF and/or activin-B alone.
577	18065398	In this system, activin, normally an endoderm inducer, caused an 80% decrease in the Foxa2-positive endoderm fraction, whereas follistatin increased the Foxa2-positive endoderm fraction to 78%.
578	18065398	Long-term differentiation displays a twofold reduction in hepatic gene expression and threefold reduction in hepatic protein expression of activin-treated cells compared with follistatin-treated cells.
579	18065398	In this system, activin, normally an endoderm inducer, caused an 80% decrease in the Foxa2-positive endoderm fraction, whereas follistatin increased the Foxa2-positive endoderm fraction to 78%.
580	18065398	Long-term differentiation displays a twofold reduction in hepatic gene expression and threefold reduction in hepatic protein expression of activin-treated cells compared with follistatin-treated cells.
581	18223258	Smad and p38 MAP kinase-mediated signaling of proteoglycan synthesis in vascular smooth muscle.
582	18223258	This pathway was investigated using the activin receptor-like kinase 5 (ALK5) inhibitor SB431542 and inhibitors of p38 MAP kinase as a possible downstream or alternative mediator.
583	18223258	TGF-beta stimulated and SB431542 inhibited the phosphorylation of Smad2/3.
584	18223258	Two different p38 MAP kinase inhibitors, SB203580 and SB202190, but not the inactive analogue SB202474, concentration-dependently blocked TGF-beta-mediated [(35)S]sulfate incorporation.
585	18223258	TGF-beta increased [(3)H]glucosamine incorporation into glycosaminoglycans by 180% and [(35)S]Met/Cys incorporation into proteoglycan core proteins by 35% with both effects completely inhibited by SB431542.
586	18223258	Blocking both Smad2/3 and p38 MAP kinase pathways prevented the effect of TGF-beta to increase proteoglycan to LDL binding.
587	18223258	TGF-beta mediates its effects on proteoglycan synthesis in VSMCs via the ALK5/Smad2/3 phosphorylation pathway as well as via the p38 MAP kinase signaling cascade.
588	18506084	Up-regulation of JAM-1 in AR42J cells treated with activin A and betacellulin and the diabetic regenerating islets.
589	18506084	The expression level of JAM-1 showed an up-regulation in the mRNA level after 3 hours and in the protein level after 24 hours in [activin A + betacellulin]-treated AR42J cells.
590	18506084	The expressions of its signaling molecules, PAR-3 and atypical PKC lambda, also increased after the addition of activin A + betacellulin.
591	18506084	When JAM-1 was over-expressed in [activin A + betacellulin]-treated AR42J cells, tagged-JAM-1 was observed in cytoplasm as vesicular structures and JAM-1 was colocalized with Rab3B and Rab13, members of the Rab family expressed at tight junctions.
592	18506084	Up-regulation of JAM-1 in AR42J cells treated with activin A and betacellulin and the diabetic regenerating islets.
593	18506084	The expression level of JAM-1 showed an up-regulation in the mRNA level after 3 hours and in the protein level after 24 hours in [activin A + betacellulin]-treated AR42J cells.
594	18506084	The expressions of its signaling molecules, PAR-3 and atypical PKC lambda, also increased after the addition of activin A + betacellulin.
595	18506084	When JAM-1 was over-expressed in [activin A + betacellulin]-treated AR42J cells, tagged-JAM-1 was observed in cytoplasm as vesicular structures and JAM-1 was colocalized with Rab3B and Rab13, members of the Rab family expressed at tight junctions.
596	18506084	Up-regulation of JAM-1 in AR42J cells treated with activin A and betacellulin and the diabetic regenerating islets.
597	18506084	The expression level of JAM-1 showed an up-regulation in the mRNA level after 3 hours and in the protein level after 24 hours in [activin A + betacellulin]-treated AR42J cells.
598	18506084	The expressions of its signaling molecules, PAR-3 and atypical PKC lambda, also increased after the addition of activin A + betacellulin.
599	18506084	When JAM-1 was over-expressed in [activin A + betacellulin]-treated AR42J cells, tagged-JAM-1 was observed in cytoplasm as vesicular structures and JAM-1 was colocalized with Rab3B and Rab13, members of the Rab family expressed at tight junctions.
600	18506084	Up-regulation of JAM-1 in AR42J cells treated with activin A and betacellulin and the diabetic regenerating islets.
601	18506084	The expression level of JAM-1 showed an up-regulation in the mRNA level after 3 hours and in the protein level after 24 hours in [activin A + betacellulin]-treated AR42J cells.
602	18506084	The expressions of its signaling molecules, PAR-3 and atypical PKC lambda, also increased after the addition of activin A + betacellulin.
603	18506084	When JAM-1 was over-expressed in [activin A + betacellulin]-treated AR42J cells, tagged-JAM-1 was observed in cytoplasm as vesicular structures and JAM-1 was colocalized with Rab3B and Rab13, members of the Rab family expressed at tight junctions.
604	18951876	Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells.
605	18951876	In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway.
606	18951876	Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1.
607	18951876	These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.
608	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
609	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
610	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
611	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
612	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
613	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
614	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
615	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
616	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
617	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
618	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
619	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
620	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
621	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
622	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
623	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
624	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
625	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
626	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
627	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
628	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
629	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
630	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
631	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
632	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
633	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
634	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
635	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
636	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
637	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
638	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
639	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
640	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
641	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
642	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
643	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
644	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
645	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
646	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
647	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
648	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
649	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
650	19128983	Adiponectin upregulates monocytic activin A but systemic levels are not altered in obesity or type 2 diabetes.
651	19128983	Adiponectin and activin A reduce foam cell formation and adiponectin activates the p38 MAPK pathway that is well described to induce activin A.
652	19128983	Therefore, it was analyzed whether adiponectin alters activin A in primary human monocytes.
653	19128983	Adiponectin dose- and time-dependently induced activin A in the supernatant, and the maximal amount was observed after 12h of incubation.
654	19128983	Adiponectin-stimulated release of activin A was blocked by a p38 MAPK inhibitor.
655	19128983	Furthermore, activin A did not correlate to systemic adiponectin, body mass index, waist to hip ratio or C-reactive protein.
656	19128983	These findings indicate that adiponectin upregulates monocytic activin A release via the p38 MAPK pathway, and this may in part explain the immunoregulatory and antiatherosclerotic effects of this adipokine.
657	19295913	Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.
658	19295913	To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/-) mice fed a standard chow.
659	19295913	In contrast, Mstn(-/-) mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp.
660	19295913	To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle.
661	19295913	We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet.
662	19295913	Our results demonstrate that Mstn(-/-) mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/-) mice is an indirect result of metabolic changes in skeletal muscle.
663	19395281	Endoglin is an accessory receptor molecule that, in association with transforming growth factor beta (TGF-beta) family receptors Types I and II, binds TGF-beta1, TGF-beta3, activin A, bone morphogenetic protein (BMP)-2 and BMP-7, regulating TGF-beta dependent cellular responses.
664	19544420	Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments.
665	19582775	Role of Smad3, acting independently of transforming growth factor-beta, in the early induction of Wnt-beta-catenin signaling by parathyroid hormone in mouse osteoblastic cells.
666	19582775	We showed previously that PTH interacts with the canonical Wnt-beta-catenin signaling pathway via the transforming growth factor (TGF)-beta signaling molecule, Smad3, to modulate osteoblast differentiation and apoptosis.
667	19582775	Here, we examined which actions of Smad3 are TGF-beta-independent in stimulating the osteoblast phenotype and PTH-induced Wnt-beta-catenin signaling.
668	19582775	For this, the TGF-beta receptor type 1 [activin receptor-like kinase (ALK5)] inhibitor (SB431542), and a Smad3 mutant in which the site normally phosphorylated by ALK5 is mutated from SSVS to AAVA, was used.
669	19582775	PTH induced total beta-catenin and reduced phosphorylated beta-catenin levels at 1, 6, and 24 h in mouse osteoblastic MC3T3-E1 cells.
670	19582775	Transient transfection of Smad3AAVA inhibited the PTH induction of total beta-catenin and reduction of phosphorylated beta-catenin levels at 6 and 24 h, but not at 1 h, indicating that the early effects occur independently of TGF-beta receptor signaling.
671	19582775	On the other hand, MC3T3-E1 cell clones in which Smad3AAVA was stably expressed demonstrated elevated beta-catenin levels, although alkaline phosphatase (ALP) activity and mineralization were unaltered.
672	19582775	In contrast, MC3T3-E1 cell clones in which wild-type Smad3 was stably expressed exhibited increased ALP activity and mineralization that were decreased by the ALK5 inhibitor, SB431542, although the beta-catenin levels induced in these cells were not modulated.
673	19582775	In conclusion, the present study indicates that PTH induces osteoblast beta-catenin levels via Smad3 independently of, and dependently on, TGF-beta in the early and later induction phases, respectively.
674	19668253	The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity.
675	20007937	First-trimester follistatin-like-3 levels in pregnancies complicated by subsequent gestational diabetes mellitus.
676	20007937	OBJECTIVE To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM).
677	20398888	Two of these are VLDLR and INHBE, which showed significant increase in expression after ER stress in B cells and in primary fibroblasts.
678	20571025	Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor.
679	20571025	One component of classical G-protein-coupled receptor (GPCR) signaling invokes transactivation of protein tyrosine kinase receptors such as the epidermal growth factor receptor.
680	20571025	We have used the model of proteoglycan synthesis to demonstrate that the signaling paradigm of GPCR signaling can be extended to include the transactivation of serine/threonine receptor, specifically the TGF-beta type I receptor (TbetaRI) also known as activin-like kinase (ALK) V.
681	20571025	Thrombin stimulated elongation of GAG chains and increased proteoglycan core protein expression and these responses were blocked by the TbetaRI antagonist, SB431542 and TbetaRI siRNA knockdown, as well as several protease-activated receptor (PAR)-1 antagonists.
682	20571025	The canonical downstream response to TGF-beta is increased C-terminal phosphorylation of the transcription factor Smad2 generating phospho-Smad2C (phosphorylation of Smad2 C-terminal region).
683	20571025	The proteolytically inactive thrombin mimetic thrombin-receptor activating peptide also stimulated an increase in cytosolic phospho-Smad2C.
684	20803090	Transcription factor 7-like 2 (TCF7L2) regulates activin receptor-like kinase 1 (ALK1)/Smad1 pathway for development of diabetic nephropathy.
685	20803090	This study aims to elucidate molecular interactions between activin receptor-like kinase 1 (ALK1)/Smad1 signaling pathway and transcription factor 7-like 2 (TCF7L2) in the progression of DN in vitro and in vivo.
686	20803090	The expressions of TCF7L2 and ALK1 were induced by advanced glycation end products (AGEs) in parallel with Smad1, phosphorylated Smad1 (pSmad1), and alpha-smooth muscle actin (α-SMA) through TGF-β1 in cultured mesangial cells.
687	20803090	The binding of TCF7L2 to ALK1 promoter was confirmed by chromatin immunoprecipitation assay.
688	20803090	Furthermore, TCF7L2 induced promoter activity of ALK1.
689	20803090	AGEs and TGF-β1 induced a marked increase in TCF7L2 expression in parallel with ALK1.
690	20803090	Overexpression of TCF7L2 increased the expressions of ALK1 and Smad1.
691	20803090	Inversely, TCF7L2 knockdown by siRNA suppressed α-SMA expression as well as ALK1 and Smad1.
692	20803090	The iNOS transgenic mice (iNOS-Tgm), which developed diabetic glomerulosclerosis resembling human diabetic nephropathy, exhibited markedly increased expressions of ALK1, TCF7L2, Smad1, pSmad1, and α-SMA in glomeruli in association with mesangial matrix expansion.
693	20803090	These results provide a new evidence that the TCF7L2/ALK1/Smad1 pathway plays a key role in the development of DN.
694	20803090	Transcription factor 7-like 2 (TCF7L2) regulates activin receptor-like kinase 1 (ALK1)/Smad1 pathway for development of diabetic nephropathy.
695	20803090	This study aims to elucidate molecular interactions between activin receptor-like kinase 1 (ALK1)/Smad1 signaling pathway and transcription factor 7-like 2 (TCF7L2) in the progression of DN in vitro and in vivo.
696	20803090	The expressions of TCF7L2 and ALK1 were induced by advanced glycation end products (AGEs) in parallel with Smad1, phosphorylated Smad1 (pSmad1), and alpha-smooth muscle actin (α-SMA) through TGF-β1 in cultured mesangial cells.
697	20803090	The binding of TCF7L2 to ALK1 promoter was confirmed by chromatin immunoprecipitation assay.
698	20803090	Furthermore, TCF7L2 induced promoter activity of ALK1.
699	20803090	AGEs and TGF-β1 induced a marked increase in TCF7L2 expression in parallel with ALK1.
700	20803090	Overexpression of TCF7L2 increased the expressions of ALK1 and Smad1.
701	20803090	Inversely, TCF7L2 knockdown by siRNA suppressed α-SMA expression as well as ALK1 and Smad1.
702	20803090	The iNOS transgenic mice (iNOS-Tgm), which developed diabetic glomerulosclerosis resembling human diabetic nephropathy, exhibited markedly increased expressions of ALK1, TCF7L2, Smad1, pSmad1, and α-SMA in glomeruli in association with mesangial matrix expansion.
703	20803090	These results provide a new evidence that the TCF7L2/ALK1/Smad1 pathway plays a key role in the development of DN.
704	21076077	Peroxisome proliferators-activated receptor gamma (PPARG) ligands improve insulin sensitivity in type 2 diabetes and polycystic ovarian syndrome (PCOS).
705	21076077	Despite clinical studies showing normalization of pituitary responsiveness to gonadotropin-releasing hormone (GnRH) in patients with PCOS, the precise role of PPARG in regulating the hypothalamic-pituitary-gonadal axis remains unclear.
706	21076077	In mouse LbetaT2 immortalized gonadotrophs, rosiglitazone treatment inhibited GnRH stimulation of the stress kinases p38MAPK and MAPKs/JNKs, but did not alter activation of ERKs, both in the presence and absence of activin.
707	21076077	Furthermore, p38MAPK signaling was critical for both Lhb and Fshb promoter activity, and rosiglitazone suppressed the GnRH-mediated induction of Lhb and Fshb mRNA.
708	21076077	Depletion of PPARG using a lentivirally encoded short hairpin RNA abolishes the effect of rosiglitazone to suppress activation of JNKs and induction of the transcription factors EGR1 and FOS as well as the gonadotropin genes Lhb and Fshb.
709	21076077	Lastly, we show conditional knockout of Pparg in pituitary gonadotrophs caused an increase in luteinizing hormone levels in female mice, a decrease in follicle-stimulating hormone in male mice, and a fertility defect characterized by reduced litter size.
710	21191111	PACAP increases alpha-subunit (Cga) and Lhb mRNAs, and it stimulates the transcription of follistatin (Fst) that, in turn, restrains activin signaling to repress Fshb and gonadotropin-releasing hormone-receptor (Gnrhr) expression as well as other activin-responsive genes.
711	21191111	At birth, pituitary PACAP declines and pituitary follistatin levels decrease, which together with increased gonadotropin-releasing hormone secretion allow Gnrhr and Fshb to increase and facilitate activation of the newborn gonads.
712	21191111	Changes in Adcyap1 expression levels in the adult pituitary may contribute to the selective rise in follicle-stimulating hormone (FSH) from age 20-30 days to the midcycle surge and to the secondary increase in FSH that occurs before estrus.
713	21353873	A type I receptor, which is a component of the complex, is known as an activin receptor-like kinase (ALK); currently seven ALKs (ALK1-ALK7) have been identified in humans.
714	21353873	Activins signaling, which is mediated by ALK4 and 7 together with ActRIIA and IIB, plays a critical role in glucose-stimulated insulin secretion, development/neogenesis, and glucose homeostatic control of pancreatic endocrine cells; the insulin gene is regulated by these signaling pathways via ALK7, which is a receptor for Activins AB and B and Nodal.
715	21353874	Activin receptor type IIB (ActRIIB) belongs to a type II transforming growth factor-β (TGF-β) serine/threonine kinase receptor family which is integral to the activin and myostatin signaling pathway.
716	21353874	Actvin and myostatin bind to activin type II receptors (ActRIIA and ActRIIB), and the glycine-serine-rich domains of type I receptors are phosphorylated by type II receptors.
717	21353874	Activin receptor type IIB (ActRIIB) belongs to a type II transforming growth factor-β (TGF-β) serine/threonine kinase receptor family which is integral to the activin and myostatin signaling pathway.
718	21353874	Actvin and myostatin bind to activin type II receptors (ActRIIA and ActRIIB), and the glycine-serine-rich domains of type I receptors are phosphorylated by type II receptors.
719	21865351	Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males.
720	22023380	Mice were fed a diet containing 60% kcal from fat for 12 weeks followed by treatment with a soluble MSTN receptor derived from the activin receptor type IIB extracellular domain.
721	22056147	Treatment with activin A and a GSK3β inhibitor enhanced efficient endodermal differentiation, and then combined treatment with retinoic acid, a bone morphogenic protein inhibitor, and a transforming growth factor-β (TGF-β) inhibitor induced efficient differentiation of pancreatic progenitor cells from definitive endoderm.
722	22202163	Unlike activin A, CnP inhibited activation of cultured stellate cells and reduced the production of collagen.
723	22202163	In pancreatic sections obtained from 6-wk-old GK rats, CD68-positive macrophages and glial fibrillary acidic protein- and α-smooth muscle actin-positive stellate cells infiltrated into islets.
724	22306733	Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury.
725	22306733	A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor.
726	22393251	Here, we inhibited MSTN in adult mice with a soluble activin receptor type IIB and analysed the incorporation of new nuclei using 5-bromo-2-deoxyuridine (BrdU) labelling by isolating individual myofibres.
727	22579779	The constitutively activating mutation (R206H) of the BMP type 1 receptor, activin A type 1 receptor/activin-like kinase 2 (ACVR1/ALK2), underlies the molecular pathogenesis of fibrodysplasia ossificans progressiva (FOP) in which heterotopic ossification occurs in muscle tissue.
728	22579779	Transcriptional activity of the BMP-2 signaling molecules, Smad1/5, was increased even in the absence of exogenous BMP-2.
729	22579779	Endogenous BMP-2 levels positively correlated with Tmem119 levels.
730	22579779	A BMP-2/4 neutralizing antibody and dorsomorphin, an ALK2 inhibitor, antagonized Tmem119-enhanced alkaline phosphatase (ALP) levels.
731	22579779	Tmem119 siRNA antagonized the BMP-2-induced ALP and osteocalcin, but not Runx2 and Osterix, mRNAs, in C2C12 cells.
732	22579779	In conclusion, Tmem119 levels were increased by the FOP-associated constitutively activating ALK2 mutation in myoblasts.
733	22579779	The data show that Tmem119 promotes the differentiation of myoblasts into osteoblasts and the interaction with the BMP signaling pathway likely occurs downstream of Runx2 and Osterix in myoblasts.
734	22596054	The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity.
735	22596054	A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle.
736	22596054	MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity.
737	22596054	These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes.
738	22652787	Hepatic oval cells can be redirected to the beta-cell linage by an appropriate combination of high extracellular glucose, specific extracellular matrix proteins (laminin and fibronectin), cytokines (activin A), and the expression of several differentiation-related transcription factors (Pdx-1, Ngn-3, MafA).
739	22750100	Combined treatment of CM and OA further regulates a set of downstream NF-κB target genes including angiopoietin-1, activin A, and MMP-1, all critically involved in SMC dysfunction.
740	22915381	Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid.
741	22919367	Here, we present an efficacy strategy for the differentiation of mouse ES cells into insulin-producing cells (IPCs) by a two-step differentiation protocol comprising of (i) the formation of definitive endoderm in monolayer culture by activin A, and (ii) this monolayer endoderm being induced to differentiate into IPCs by nicotinamide, insulin, and laminin.
742	23116663	Increased glucose and insulin had no effect on base-line activin A secretion by BMNPs in culture, but pre-treatment with insulin blocked the TNF-α induced release of activin A.
743	23116663	Furthermore, regulation of neutrophil activin A release by insulin may also play a role in the inflammation associated with T2D.
744	23116663	Increased glucose and insulin had no effect on base-line activin A secretion by BMNPs in culture, but pre-treatment with insulin blocked the TNF-α induced release of activin A.
745	23116663	Furthermore, regulation of neutrophil activin A release by insulin may also play a role in the inflammation associated with T2D.
746	23754846	It has been previously shown that elastin degradation products work synergistically with transforming growth factor-beta 1 (TGF-β1) to induce osteogenesis in vascular smooth muscle cells.
747	23754846	Thus, the goal of this study was to analyse the effects of high concentration of glucose, elastin peptides and TGF-β1 on bone-specific markers like alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2).
748	23754846	We demonstrated using relative gene expression and specific protein assays that elastin degradation products in the presence of high glucose cause the increase in expression of the specific elastin-laminin receptor-1 (ELR-1) and activin receptor-like kinase-5 (ALK-5) present on the surface of the vascular cells, in turn leading to overexpression of typical osteogenic markers like ALP, OCN and RUNX2.
749	23754846	In conclusion, our results indicate that glucose plays an important role in amplifying the osteogenesis induced by elastin peptides and TGF-β1, possibly by activating the ELR-1 and ALK-5 signalling pathways.
750	23838169	In type 1 diabetes, muscle wasting essentially results from insulin deficiency and this induces of genes involved in the ubiquitin proteasome pathway.
751	23838169	Decreased insulin responsiveness has been attributed to defects in the insulin signaling pathways secondary to inflammation (e.g., NF-κB activation and elevated levels of TNF-α, IL-1 and IL-6), metabolic acidosis, increased circulating free fatty acids and glucotoxicity.
752	23838169	Furthermore, emerging pathways, such as myostatin/activin A system are beginning to be uncovered.
753	23987834	Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and Bærum Cardiovascular Diabetes (ABCD) cohort study.