LIVIVO - Search results -

Search results

Result 1 - 10 of total 138

Search options

Article ; Online: Adventures with insulin in the islets of Langerhans.

Steiner, Donald F

2011 Volume 286, Issue 20, Page(s) 17399–17421

Abstract: Insulin is a small but beautifully organized protein with a unique two-chain structure, the first protein to be sequenced. The mechanism of its biosynthesis invited much initial speculation but was finally clarified by the discovery of proinsulin, its ... ...

Abstract	Insulin is a small but beautifully organized protein with a unique two-chain structure, the first protein to be sequenced. The mechanism of its biosynthesis invited much initial speculation but was finally clarified by the discovery of proinsulin, its single-chain precursor. The rich present-day field of protein precursor processing via post-translational proteolysis within the secretory pathway arose in the early 1970s as an offshoot of studies on insulin biosynthesis, which provided a novel paradigm for the generation of many other small neuroendocrine peptides. Before long, this mechanism was also found to play a role in the production of a much wider spectrum of proteins traversing the secretory pathway (receptors, growth factors, blood-clotting components, and even many viral envelope proteins) occurring in almost all eukaryotic cells. Indeed, yeast provided a key clue in the search for the proprotein convertases, the endoproteases that work along with carboxypeptidases and other modifying enzymes, such as the amidating enzyme complex (PAM), in converting inactive or less active precursor proteins into their fully active peptide products. In this "Reflections" article, I have tried to recount the people and events in my life that led to my involvement first in basic biochemical research and then on to insulin, proinsulin, and many relevant related areas that continue to fascinate and challenge my colleagues and me, as well as many other biomedical scientists today, as diabetes mellitus increasingly threatens human health throughout our contemporary world.
MeSH term(s)	Animals ; Biochemistry/history ; Biochemistry/methods ; History, 20th Century ; History, 21st Century ; Humans ; Insulin/history ; Insulin/metabolism ; Islets of Langerhans/metabolism
Chemical Substances	Insulin
Language	English
Publishing date	2011-03-28
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.X111.244764
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: On the discovery of precursor processing.

Steiner, Donald F

Methods in molecular biology (Clifton, N.J.)

2011 Volume 768, Page(s) 3–11

Abstract: Studies of the biosynthesis of insulin in a human insulinoma beginning in 1965 provided the first evidence for a precursor of insulin, the first such prohormone to be identified. Further studies with isolated rat islets then confirmed that the precursor ... ...

Abstract	Studies of the biosynthesis of insulin in a human insulinoma beginning in 1965 provided the first evidence for a precursor of insulin, the first such prohormone to be identified. Further studies with isolated rat islets then confirmed that the precursor became labeled more rapidly than insulin and later was converted to insulin by a proteolytic processing system located mainly within the secretory granules of the beta cell and was then stored or secreted. The precursor was designated "proinsulin" in 1967 and was isolated and sequenced from beef and pork sources. These structural studies confirmed that the precursor was a single polypeptide chain which began with the B chain of insulin, continued through a connecting segment of 30-35 amino acids and terminated with the A chain. Paired basic residues were identified at the sites of excision of the C-peptide. Human proinsulin and C-peptide were then similarly obtained and sequenced. The human C-peptide assay was developed and provided a useful tool for measuring insulin levels indirectly in diabetics treated with insulin. The discovery of other precursor proteins for a variety of peptide hormones, neuropeptides, or plasma proteins then followed, with all having mainly dibasic cleavage sites for processing. The subsequent discovery of a similar biosynthetic pathway in yeast led to the identification of eukaryotic families of specialized processing subtilisin-like endopeptidases coupled with carboxypeptidase B-like exopeptidases. Most neuroendocrine peptides are processed by two specialized members of this family - PC2 and/or PC1/3 - followed by carboxypeptidase E (CPE). This brief report concentrates mainly on the role of insulin biosynthesis in providing a useful early paradigm of precursor processing in the secretory pathway.
MeSH term(s)	Animals ; C-Peptide/biosynthesis ; Carboxypeptidase H/metabolism ; Cattle ; History, 20th Century ; Humans ; Insulin/biosynthesis ; Insulin-Secreting Cells/enzymology ; Insulinoma/metabolism ; Neuropeptides/metabolism ; Proinsulin/biosynthesis ; Proprotein Convertase 1/metabolism ; Proprotein Convertase 2/metabolism ; Protein Precursors/history ; Protein Precursors/metabolism ; Protein Processing, Post-Translational/physiology ; Rats ; Saccharomyces cerevisiae ; Swine
Chemical Substances	C-Peptide ; Insulin ; Neuropeptides ; Protein Precursors ; Proinsulin (9035-68-1) ; Carboxypeptidase H (EC 3.4.17.10) ; Proprotein Convertase 1 (EC 3.4.21.93) ; Proprotein Convertase 2 (EC 3.4.21.94)
Language	English
Publishing date	2011
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-61779-204-5_1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Opportunities, Challenges, and Strategies for Engaging Family in Diabetes and Hypertension Management: A Qualitative Study.

Fort, Meredith P / Steiner, John F / Santos, Cornelia / Moore, Kelly R / Villaverde, Maria de / Nease, Donald E / Ortega, Debora / Manson, Spero M

Journal of health care for the poor and underserved

2021 Volume 31, Issue 2, Page(s) 827–844

Abstract: Family engagement may improve disease management, yet little is known about this topic as it relates to underrepresented minorities who receive care in low-resource primary care settings. This study aimed to explore family engagement in diabetes and ... ...

Abstract	Family engagement may improve disease management, yet little is known about this topic as it relates to underrepresented minorities who receive care in low-resource primary care settings. This study aimed to explore family engagement in diabetes and hypertension management at an Urban Indian Health Organization to identify opportunities and challenges, and inform care strategies. We employed semi-structured interviews, genograms, eco-maps, and timelines, among 23 English- and Spanish-speaking American Indian and Latino adults with a dual diagnosis of type 2 diabetes and hypertension and 13 family members. Using thematic analysis, we found that family support is not always available, patients have difficulty sharing medical information, and family often live far away. Conversely, opportunities to leverage included a desire for increased engagement, motivation from the younger generation, prevention within the family, outreach to family members with the same conditions, and learning from elders and ancestors. Implications for programs, clinical care, and research are discussed.
MeSH term(s)	Aged ; Diabetes Mellitus, Type 2/therapy ; Family ; Humans ; Hypertension/therapy ; Primary Health Care ; Qualitative Research
Language	English
Publishing date	2021-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1142637-8
ISSN	1548-6869 ; 1049-2089
ISSN (online)	1548-6869
ISSN	1049-2089
DOI	10.1353/hpu.2020.0063
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3605: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 493: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: The proinsulin C-peptide--a multirole model.

Steiner, Donald F

Experimental diabesity research

2004 Volume 5, Issue 1, Page(s) 7–14

Abstract: The C-peptide links the insulin A and B chains in proinsulin, providing thereby a means to promote their efficient folding and assembly in the endoplasmic reticulum during insulin biosynthesis. It then facilitates the intracellular transport, sorting, ... ...

Abstract	The C-peptide links the insulin A and B chains in proinsulin, providing thereby a means to promote their efficient folding and assembly in the endoplasmic reticulum during insulin biosynthesis. It then facilitates the intracellular transport, sorting, and proteolytic processing of proinsulin into biologically active insulin in the maturing secretory granules of the beta cells. These manifold functions impose significant constraints on the C-peptide structure that are conserved in evolution. After cleavage of proinsulin, the intact C-peptide is stored with insulin in the soluble phase of the secretory granules and is subsequently released in equimolar amounts with insulin, providing a useful independent indicator of insulin secretion. This brief review highlights many aspects of its roles in biosynthesis, as a prelude to consideration of its possible additional role(s) as a physiologically active peptide after its release with insulin into the circulation in vivo.
MeSH term(s)	Amino Acid Sequence ; Animals ; C-Peptide/genetics ; C-Peptide/physiology ; Evolution, Molecular ; Humans ; Insulin/biosynthesis ; Molecular Conformation ; Molecular Sequence Data ; Proinsulin/genetics ; Proinsulin/physiology ; Protein Processing, Post-Translational
Chemical Substances	C-Peptide ; Insulin ; Proinsulin (9035-68-1)
Language	English
Publishing date	2004-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2159651-7
ISSN	1543-8600
ISSN	1543-8600
DOI	10.1080/15438600490424389
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 5807: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Disparate patterns of hospitalisation reflect unmet needs and persistent ethnic inequalities in mental health care: the Scottish health and ethnicity linkage study.

Bansal, Narinder / Bhopal, Raj / Netto, Gina / Lyons, Donald / Steiner, Markus F C / Sashidharan, Sashi P

Ethnicity & health

2013 Volume 19, Issue 2, Page(s) 217–239

Abstract: Objectives: The presence and extent of mental health inequalities in Scotland is unclear. We investigated ethnic variations in psychiatric hospitalisations and compulsory treatment in relation to socioeconomic indicators.: Design: In a retrospective ... ...

Abstract	Objectives: The presence and extent of mental health inequalities in Scotland is unclear. We investigated ethnic variations in psychiatric hospitalisations and compulsory treatment in relation to socioeconomic indicators. Design: In a retrospective cohort study design, using data linkage methods, we examined ethnic variations in psychiatric [any psychiatric, mood (affective), and psychotic disorders) hospitalisations and use of the Mental Health (Care and Treatment) (Scotland) Act 2003 (Emergency Detentions (ED), Short-Term Detentions (STD) and Compulsory Treatment Orders (CTO)] using age (and sex for compulsory treatment), car ownership, and housing tenure adjusted risk ratios (RR). 95% CIs for the data below exclude the reference White Scottish group value (100). Results: Compared to the White Scottish population, Other White British men and women had lower hospitalisation from any psychiatric disorder (RR = 77.8, 95% CI: 71.0-85.2 and 85.8, 95% CI: 79.3-92.9), mood disorder (91.2, 95% CI: 86.9-95.8 and 83.6, 95% CI: 75.1-93.1), psychotic disorder (67.1, 95% CI: 59.9-75.2 and 78.5, 95% CI: 67.6-91.1), CTO (84.6, 95% CI: 72.4-98.9) and STD (88.2, 95% CI: 78.6-99.0). Any Mixed Background women had higher hospitalisation from any psychiatric disorder (137.2, 95% CI: 110.9-169.6) and men and women had a higher risk of psychotic disorder (200.6, 95% CI: 105.7-380.7 and 175.5, 95% CI: 102.3-301.2), CTO (263.0, 95% CI: 105.4-656.3), ED (245.6, 95% CI: 141.6-426.1) and STD (311.7, 95% CI: 190.2-510.7). Indian women had lower risk of any psychiatric disorder (43.2, 95% CI: 28.0-66.7). Pakistani men had lower risk of any psychiatric disorder (78.7, 95% CI: 69.3-89.3), and higher risk of mood disorders (117.5, 95% CI: 100.2-137.9). Pakistani women had similar risk of any psychiatric and mood disorder however, a twofold excess risk of psychotic disorder (227.3, 95% CI: 195.8-263.8). Risk of STD was higher in South Asians (136.9, 95% CI: 109.0-171.9). Chinese men and women had the lowest risk of hospitalisation for any psychiatric disorder (35.3, 95% CI: 23.2-53.7 and 44.5, 95% CI: 30.3-65.5) and mood disorder (51.5, 95% CI: 31.0-85.4 and 47.5, 95% CI: 23.2-97.4) but not psychotic disorders and higher risk for CTO (181.4, 95% CI: 121.0-271.0). African women had higher risk of any psychiatric disorder (139.4, 95% CI: 119.0-163.2). African men and women had the highest risk for psychotic disorders (230.8, 95% CI: 177.8-299.5 and 240.7, 95% CI: 163.8-353.9) and were also overrepresented in STD (214.3, 95% CI: 122.4-375.0) and CTO (486.6, 95% CI: 231.9-1021.1). Differences in hospitalisations were not fully attenuated when adjusted for car ownership and housing tenure and the effect of these adjustments varied by ethnic group. Conclusion: Our data show disparate patterns of psychiatric hospitalisations by ethnic group in Scotland providing new observations concerning the mental health care experience of Chinese, Mixed background and White subgroups not fully explained by socioeconomic indicators. For South Asian and Chinese groups in particular, our data indicate under and late utilisation of mental health services. These data call for monitoring and review of services.
MeSH term(s)	Adult ; Cohort Studies ; Data Collection ; Female ; Health Status Disparities ; Healthcare Disparities/ethnology ; Healthcare Disparities/statistics & numerical data ; Hospitalization/statistics & numerical data ; Humans ; Male ; Mental Disorders/ethnology ; Mental Disorders/therapy ; Mental Health Services/statistics & numerical data ; Middle Aged ; Poisson Distribution ; Racial Groups/statistics & numerical data ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Scotland/epidemiology ; Socioeconomic Factors
Language	English
Publishing date	2013-07-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1497968-8
ISSN	1465-3419 ; 1355-7858
ISSN (online)	1465-3419
ISSN	1355-7858
DOI	10.1080/13557858.2013.814764
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5110: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Pim3 negatively regulates glucose-stimulated insulin secretion.

Vlacich, Gregory / Nawijn, Martijn C / Webb, Gene C / Steiner, Donald F

Islets

2010 Volume 2, Issue 5, Page(s) 308–317

Abstract: Pancreatic β-cell response to glucose stimulation is governed by tightly regulated signaling pathways which have not been fully characterized. A screen for novel signaling intermediates identified Pim3 as a glucose-responsive gene in the β cell, and here, ...

Abstract	Pancreatic β-cell response to glucose stimulation is governed by tightly regulated signaling pathways which have not been fully characterized. A screen for novel signaling intermediates identified Pim3 as a glucose-responsive gene in the β cell, and here, we characterize its role in the regulation of β-cell function. Pim3 expression in the β-cell was first observed through microarray analysis on glucose-stimulated murine insulinoma (MIN6) cells where expression was strongly and transiently induced. In the pancreas, Pim3 expression exhibited similar dynamics and was restricted to the β cell. Perturbation of Pim3 function resulted in enhanced glucose-stimulated insulin secretion, both in MIN6 cells and in isolated islets from Pim3-/- mice, where the augmentation was specifically seen in the second phase of secretion. Consequently, Pim3-/- mice displayed an increased glucose tolerance in vivo. Interestingly, Pim3-/- mice also exhibited increased insulin sensitivity. Glucose stimulation of isolated Pim3-/- islets resulted in increased phosphorylation of ERK1/2, a kinase involved in regulating β-cell response to glucose. Pim3 was also found to physically interact with SOCS6 and SOCS6 levels were strongly reduced in Pim3-/- islets. Overexpression of SOCS6 inhibited glucose-induced ERK1/2 activation, strongly suggesting that Pim3 regulates ERK1/2 activity through SOCS6. These data reveal that Pim3 is a novel glucose-responsive gene in the β cell that negatively regulates insulin secretion by inhibiting the activation of ERK1/2, and through its effect on insulin sensitivity, has potentially a more global function in glucose homeostasis.
MeSH term(s)	Animals ; Cell Line ; Cell Size ; Gene Expression Profiling ; Gene Expression Regulation ; Hyperglycemia ; Insulin/metabolism ; Insulin Resistance ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/cytology ; Islets of Langerhans/physiology ; MAP Kinase Signaling System ; Male ; Mice ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; Organ Culture Techniques ; Organ Specificity ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/physiology ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/physiology ; RNA, Messenger/metabolism ; Suppressor of Cytokine Signaling Proteins/genetics ; Suppressor of Cytokine Signaling Proteins/metabolism
Chemical Substances	Insulin ; Proto-Oncogene Proteins ; RNA, Messenger ; Socs6 protein, mouse ; Suppressor of Cytokine Signaling Proteins ; Pim3 protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2010-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1938-2022
ISSN (online)	1938-2022
DOI	10.4161/isl.2.5.13058
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Detection and description of small breast masses by residents trained using a standardized clinical breast exam curriculum.

Steiner, Elizabeth / Austin, Donald F / Prouser, Nancy C

Journal of general internal medicine

2007 Volume 23, Issue 2, Page(s) 129–134

Abstract: Objectives: We evaluated the effect of standardized clinical breast examination (CBE) training on residents' ability to detect a 3-mm breast mass in a silicone breast model.: Methods: In this nonrandomized controlled trial, 75 first year residents ( ... ...

Abstract	Objectives: We evaluated the effect of standardized clinical breast examination (CBE) training on residents' ability to detect a 3-mm breast mass in a silicone breast model. Methods: In this nonrandomized controlled trial, 75 first year residents (R1s) at 8 family medicine, internal medicine, and obstetrics and gynecology training programs received the intervention and second year residents (R2s) did not. Trained residency faculty taught R1s vertical strip, three-pressure method (VS3PM) CBE using a standardized curriculum, including a 1- to 2-hour online self-study with video and 2.5-hour practicum using silicone models and a trained patient surrogate. Results: Solitary mass detection: 84% by R1s, 46% by R2s (RR = 1.82, 95%CI = 1.36, 2.43, P < 0.0001). Of those finding a mass, 62% of R1s and 10% of R2s used at least 5 of 8 standardized descriptors (RR = 6.19, 95%CI = 2.06, 18.59, P = 0.001). R1s false positive findings were not statistically different from R2s (P = 0.54). Both the use of VS3PM and total time spent on CBE were independently highly predictive of finding the mass in either group. Conclusions: Most untrained primary care residents are not proficient in CBE. Standardized VS3PM CBE training improves the ability to detect and describe a small mass in a silicone breast model. Better CBE training for residents may improve the early detection of breast cancer.
MeSH term(s)	Breast Diseases/diagnosis ; Case-Control Studies ; Clinical Competence ; Curriculum ; Early Diagnosis ; False Negative Reactions ; False Positive Reactions ; Humans ; Internship and Residency ; Manikins ; Physical Examination/methods
Language	English
Publishing date	2007-12-04
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639008-0
ISSN	1525-1497 ; 0884-8734
ISSN (online)	1525-1497
ISSN	0884-8734
DOI	10.1007/s11606-007-0444-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2205: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Complementation analysis demonstrates that insulin cross-links both alpha subunits in a truncated insulin receptor dimer.

Chan, Shu Jin / Nakagawa, Satoe / Steiner, Donald F

The Journal of biological chemistry

2007 Volume 282, Issue 18, Page(s) 13754–13758

Abstract: The insulin receptor is a homodimer composed of two alphabeta half receptors. Scanning mutagenesis studies have identified key residues important for insulin binding in the L1 domain (amino acids 1-150) and C-terminal region (amino acids 704-719) of the ... ...

Abstract	The insulin receptor is a homodimer composed of two alphabeta half receptors. Scanning mutagenesis studies have identified key residues important for insulin binding in the L1 domain (amino acids 1-150) and C-terminal region (amino acids 704-719) of the alpha subunit. However, it has not been shown whether insulin interacts with these two sites within the same alpha chain or whether it cross-links a site from each alpha subunit in the dimer to achieve high affinity binding. Here we have tested the contralateral binding mechanism by analyzing truncated insulin receptor dimers (midi-hIRs) that contain complementary mutations in each alpha subunit. Midi-hIRs containing Ala(14), Ala(64), or Gly(714) mutations were fused with Myc or FLAG epitopes at the C terminus and were expressed separately by transient transfection. Immunoblots showed that R14A+FLAG, F64A+FLAG, and F714G+Myc mutant midi-hIRs were expressed in the medium but insulin binding activity was not detected. However, after co-transfection with R14A+FLAG/F714G+Myc or F64A+FLAG/F714G+Myc, hybrid dimers were obtained with a marked increase in insulin binding activity. Competitive displacement assays revealed that the hybrid mutant receptors bound insulin with the same affinity as wild type and also displayed curvilinear Scatchard plots. In addition, when hybrid mutant midi-hIR was covalently cross-linked with (125)I(A14)-insulin and reduced, radiolabeled monomer was immunoprecipitated only with anti-FLAG, demonstrating that insulin was bound asymmetrically. These results demonstrate that a single insulin molecule can contact both alpha subunits in the insulin receptor dimer during high affinity binding and this property may be an important feature for receptor signaling.
MeSH term(s)	Amino Acid Sequence/genetics ; Antigens, CD/chemistry ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Cell Line ; Dimerization ; Genetic Complementation Test ; Hartnup Disease ; Humans ; Insulin/chemistry ; Insulin/metabolism ; Mutation, Missense ; Protein Binding/genetics ; Protein Subunits/chemistry ; Protein Subunits/genetics ; Protein Subunits/metabolism ; Receptor, Insulin/chemistry ; Receptor, Insulin/genetics ; Receptor, Insulin/metabolism ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion ; Signal Transduction/genetics
Chemical Substances	Antigens, CD ; Insulin ; Protein Subunits ; Recombinant Fusion Proteins ; INSR protein, human (EC 2.7.10.1) ; Receptor, Insulin (EC 2.7.10.1)
Language	English
Publishing date	2007-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M700724200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biosynthesis of proTRH-derived peptides in prohormone convertase 1 and 2 knockout mice.

Cyr, Nicole E / Stuart, Ronald C / Zhu, Xiaorong / Steiner, Donald F / Nillni, Eduardo A

Peptides

2012 Volume 35, Issue 1, Page(s) 42–48

Abstract: Prohormone convertases (PCs) 1 and 2 are the primary endoproteases involved in the post-translational processing of proThyrotropin Releasing Hormone (proTRH) to give rise to TRH and other proposed biologically active non-TRH peptides. Previous evidence ... ...

Abstract	Prohormone convertases (PCs) 1 and 2 are the primary endoproteases involved in the post-translational processing of proThyrotropin Releasing Hormone (proTRH) to give rise to TRH and other proposed biologically active non-TRH peptides. Previous evidence suggests that PC1 is responsible for most proTRH cleavage events. Here, we used the PC1 and PC2 knockout (KO) mouse models to examine the effects of PC1 or PC2 loss on proTRH processing. The PC1KO mouse presented a decrease in five proTRH-derived peptides, whereas the PC2KO mouse showed only lesser reduction in three TRH (Gln-His-Pro), TRH-Gly (Gln-His-Pro-Gly), and the short forms preproTRH(178-184) (pFQ(7)) and preproTRH(186-199) (pSE(14)) of pFE(22) (preproTRH(178-199)). Also, PC1KO and not PC2KO showed a decrease in pEH(24) indicating that PC1 is more important in generating this peptide in the mouse, which differs from previous studies using rat proTRH. Furthermore, downstream effects on thyroid hormone levels were evident in PC1KO mice, but not PC2KO mice suggesting that PC1 plays the more critical role in producing bioactive hypophysiotropic TRH. Yet loss of PC1 did not abolish TRH entirely indicating a complementary action for both enzymes in the normal processing of proTRH. We also show that PC2 alone is responsible for catalyzing the conversion of pFE(22) to pFQ(7) and pSE(14), all peptides implicated in regulation of suckling-induced prolactin release. Collectively, results characterize the specific roles of PC1 and PC2 in proTRH processing in vivo.
MeSH term(s)	Amino Acid Sequence ; Animals ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Paraventricular Hypothalamic Nucleus/metabolism ; Peptide Fragments/biosynthesis ; Proprotein Convertase 1/deficiency ; Proprotein Convertase 1/genetics ; Proprotein Convertase 2/deficiency ; Proprotein Convertase 2/genetics ; Protein Precursors/biosynthesis ; Sequence Homology, Amino Acid ; Thyrotropin-Releasing Hormone/biosynthesis ; Triiodothyronine/biosynthesis
Chemical Substances	Peptide Fragments ; Protein Precursors ; Triiodothyronine (06LU7C9H1V) ; Thyrotropin-Releasing Hormone (5Y5F15120W) ; Proprotein Convertase 1 (EC 3.4.21.93) ; Proprotein Convertase 2 (EC 3.4.21.94)
Language	English
Publishing date	2012-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2012.02.024
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1649: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Preservation of Reduced Numbers of Insulin-Positive Cells in Sulfonylurea-Unresponsive KCNJ11-Related Diabetes.

Greeley, Siri Atma W / Zielinski, Mark C / Poudel, Ananta / Ye, Honggang / Berry, Shivani / Taxy, Jerome B / Carmody, David / Steiner, Donald F / Philipson, Louis H / Wood, Jamie R / Hara, Manami

The Journal of clinical endocrinology and metabolism

2017 Volume 102, Issue 1, Page(s) 1–5

Abstract: Context: The most common genetic cause of permanent neonatal diabetes mellitus is activating mutations in KCNJ11, which can usually be treated using oral sulfonylureas (SUs) instead of insulin injections, although some mutations are SU unresponsive. In ... ...

Abstract	Context: The most common genetic cause of permanent neonatal diabetes mellitus is activating mutations in KCNJ11, which can usually be treated using oral sulfonylureas (SUs) instead of insulin injections, although some mutations are SU unresponsive. In this work, we provide a report of the pancreatic islet endocrine cell composition and area in a patient with an SU-unresponsive KCNJ11 mutation (p.G334D), in comparison with age-matched controls. Case description: Pancreatic autopsy tissue sections from a 2-year-old female child diagnosed with KCNJ11-related diabetes at 4 days of age and 13 age-matched controls were stained with insulin, glucagon, somatostatin, pancreatic polypeptide, and Ki67 antibodies to determine islet endocrine cell composition and area. β-cell ultrastructure was assessed by electron microscopic (EM) analysis. The patient's pancreas (sampling from head to tail) revealed insulin-positive cells in all regions. The pancreatic β-cell (insulin) area was significantly reduced compared with controls: 0.50% ± 0.04% versus 1.67% ± 0.20%, respectively (P < 0.00001). There were no significant differences in α-cell (glucagon) or δ-cell (somatostatin) area. EM analysis revealed secretory granules with a dense core typical of mature β-cells as well as granules with a lighter core characteristic of immature granules. Conclusions: Our results suggest that mechanisms exist that allow preservation of β-cells in the absence of insulin secretion. It remains to be determined to what extent this reduction in β-cells may be reversible.
MeSH term(s)	Autopsy ; Biomarkers/analysis ; Blood Glucose/analysis ; Case-Control Studies ; Child, Preschool ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/metabolism ; Diabetes Mellitus/pathology ; Drug Resistance ; Female ; Humans ; Infant ; Insulin/metabolism ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/pathology ; Mutation/genetics ; Potassium Channels, Inwardly Rectifying/genetics ; Prognosis ; Sulfonylurea Compounds/pharmacology
Chemical Substances	Biomarkers ; Blood Glucose ; Insulin ; Kir6.2 channel ; Potassium Channels, Inwardly Rectifying ; Sulfonylurea Compounds
Language	English
Publishing date	2017-01-01
Publishing country	United States
Document type	Case Reports ; Comparative Study ; Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2016-2826
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.134: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito