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Ahooghalandari, Parvin
Publications (8 of 8) Show all publications
Yu, Q., Shuai, H., Ahooghalandari, P., Gylfe, E. & Tengholm, A. (2016). Glucose lowers cAMP to inhibit glucagon secretion by a direct effect on alpha cells. Paper presented at 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY. Diabetologia, 59, S266-S267
Open this publication in new window or tab >>Glucose lowers cAMP to inhibit glucagon secretion by a direct effect on alpha cells
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2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S266-S267Article in journal (Refereed) Published
Place, publisher, year, edition, pages
SPRINGER, 2016
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-322056 (URN)000398373701362 ()
Conference
52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2017-05-16Bibliographically approved
Yu, Q., Li, J., Ahooghalandari, P., Tengholm, A. & Gylfe, E. (2015). Paradoxical Ca2+ kinetics in islet-located glucagon-releasing alpha cells. Paper presented at 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 14-18, 2015, Stockholm, SWEDEN. Diabetologia, 58(Suppl. 1), S268-S269
Open this publication in new window or tab >>Paradoxical Ca2+ kinetics in islet-located glucagon-releasing alpha cells
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2015 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S268-S269Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-264916 (URN)000359820901240 ()
Conference
51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 14-18, 2015, Stockholm, SWEDEN
Note

Meeting Abstract: 550

Available from: 2015-11-04 Created: 2015-10-19 Last updated: 2017-12-01Bibliographically approved
Li, J., Yu, Q., Ahooghalandari, P., Gribble, F. M., Reimann, F., Tengholm, A. & Gylfe, E. (2015). Submembrane ATP and Ca2+ kinetics in alpha-cells: unexpected signaling for glucagon secretion. The FASEB Journal, 29(8), 3379-3388
Open this publication in new window or tab >>Submembrane ATP and Ca2+ kinetics in alpha-cells: unexpected signaling for glucagon secretion
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2015 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, no 8, p. 3379-3388Article in journal (Refereed) Published
Abstract [en]

Cytoplasmic ATP and Ca2+ are implicated in current models of glucose's control of glucagon and insulin secretion from pancreatic alpha- and beta-cells, respectively, but little is known about ATP and its relation to Ca2+ in alpha-cells. We therefore expressed the fluorescent ATP biosensor Perceval in mouse pancreatic islets and loaded them with a Ca2+ indicator. With total internal reflection fluorescence microscopy, we recorded subplasma membrane concentrations of Ca2+ and ATP ([Ca2+](pm); [ATP](pm)) in superficial alpha- and beta-cells of intact islets and related signaling to glucagon and insulin secretion by immunoassay. Consistent with ATP's controlling glucagon and insulin secretion during hypo- and hyperglycemia, respectively, the dose-response relationship for glucoseinduced [ATP](pm) generation was left shifted in alpha-cells compared to beta-cells. Both cell types showed [Ca2+](pm) and [ATP](pm) oscillations in opposite phase, probably reflecting energy-consuming Ca2+ transport. Although pulsatile insulin and glucagon release are in opposite phase, [Ca2+](pm) synchronized in the same phase between alpha- and beta-cells. This paradox can be explained by the overriding of Ca2+ stimulation by paracrine inhibition, because somatostatin receptor blockade potently stimulated glucagon release with little effect on Ca2+. The data indicate that an alpha-cell-intrinsic mechanism controls glucagon in hypoglycemia and that paracrine factors shape pulsatile secretion in hyperglycemia.

Keywords
oscillations, islet of Langerhans, signal transduction, paracrine
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-261252 (URN)10.1096/fj.14-265918 (DOI)000358796900025 ()25911612 (PubMedID)
Funder
Swedish Diabetes AssociationSwedish Research CouncilNovo Nordisk
Available from: 2015-09-01 Created: 2015-08-31 Last updated: 2018-07-31Bibliographically approved
Li, J., Yu, Q., Ahooghalandari, P., Gribble, F. M., Reimann, F., Tengholm, A. & Gylfe, E. (2015). Submembrane ATP and Ca2+ kinetics in α‑cells: unexpected signaling for glucagon secretion. The FASEB Journal, 29(8), 3379-3388
Open this publication in new window or tab >>Submembrane ATP and Ca2+ kinetics in α‑cells: unexpected signaling for glucagon secretion
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2015 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, no 8, p. 3379-3388Article in journal (Refereed) Published
Abstract [en]

Cytoplasmic ATP and Ca(2+) are implicated in current models of glucose's control of glucagon and insulin secretion from pancreatic α- and β-cells, respectively, but little is known about ATP and its relation to Ca(2+) in α-cells. We therefore expressed the fluorescent ATP biosensor Perceval in mouse pancreatic islets and loaded them with a Ca(2+) indicator. With total internal reflection fluorescence microscopy, we recorded subplasma membrane concentrations of Ca(2+) and ATP ([Ca(2+)]pm; [ATP]pm) in superficial α- and β-cells of intact islets and related signaling to glucagon and insulin secretion by immunoassay. Consistent with ATP's controlling glucagon and insulin secretion during hypo- and hyperglycemia, respectively, the dose-response relationship for glucose-induced [ATP]pm generation was left shifted in α-cells compared to β-cells. Both cell types showed [Ca(2+)]pm and [ATP]pm oscillations in opposite phase, probably reflecting energy-consuming Ca(2+) transport. Although pulsatile insulin and glucagon release are in opposite phase, [Ca(2+)]pm synchronized in the same phase between α- and β-cells. This paradox can be explained by the overriding of Ca(2+) stimulation by paracrine inhibition, because somatostatin receptor blockade potently stimulated glucagon release with little effect on Ca(2+). The data indicate that an α-cell-intrinsic mechanism controls glucagon in hypoglycemia and that paracrine factors shape pulsatile secretion in hyperglycemia.

Keywords
oscillations, islet of Langerhans, signal transduction, paracrine
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-356527 (URN)10.1096/fj.14-265918 (DOI)25911612 (PubMedID)
Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2018-10-10Bibliographically approved
Ahooghalandari, P., Hanke, N., Thorpe, M., Witte, A., Messinger, J. & Hellman, L. (2013). Mutations in Arg143 and Lys192 of the Human Mast Cell Chymase Markedly Affect the Activity of Five Potent Human Chymase Inhibitors. PLoS ONE, 8(6), e65988
Open this publication in new window or tab >>Mutations in Arg143 and Lys192 of the Human Mast Cell Chymase Markedly Affect the Activity of Five Potent Human Chymase Inhibitors
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e65988-Article in journal (Refereed) Published
Abstract [en]

Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-208169 (URN)10.1371/journal.pone.0065988 (DOI)000322361200045 ()
Available from: 2013-09-24 Created: 2013-09-24 Last updated: 2017-12-06Bibliographically approved
Fossum, C., Hjertner, B., Olofsson, K. M., Lindberg, R., Ahooghalandari, P., Camargo, M. M., . . . Nostell, K. (2012). Expression of tlr4, md2 and cd14 in equine blood leukocytes during endotoxin infusion and in intestinal tissues from healthy horses. Veterinary Immunology and Immunopathology, 150(3-4), 141-148
Open this publication in new window or tab >>Expression of tlr4, md2 and cd14 in equine blood leukocytes during endotoxin infusion and in intestinal tissues from healthy horses
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2012 (English)In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 150, no 3-4, p. 141-148Article in journal (Refereed) Published
Abstract [en]

The expression of tlr4, md2 and cd14 was studied in equine blood leukocytes and in intestinal samples using real time PCR. The stability of three commonly used reference genes, glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxantine ribosyltransferase (HPRT) and succinate dehydrogenase complex subunit A (SDHA), was evaluated using qbase(PLUS). The equine peripheral blood mononuclear cells (eqPBMC) examined were either stimulated in vitro with Phorbol 12-myristate 13-acetate (PMA) and ionomycin or with the CpG oligodeoxynuclotide 2216 (CpG-ODN 2216) or obtained from horses before, during and after infusion of endotoxin. Intestinal tissue from healthy horses was sampled at ileum, right dorsal colon and rectum. Ranking of the three reference genes used for normalisation identified the combination HPRT/SDHA as most suitable both when determined ex vivo in leukocytes obtained from experimentally induced endotoxaemia and in eqPBMC activated in vitro while HPRT/GAPDH were most appropriate for the intestinal samples. The relative amounts of mRNA for TLR4 and MD-2 increased threefold during in vitro activation of the cells with CpG-ODN 2216 but was decreased in cultures stimulated with PMA/ionomycin. A transient elevation in the transcription of tlr4 and md2 was also evident for equine blood leukocytes following endotoxaemia. The levels of mRNA for CD14 on the other hard remained unaffected both during the induction of endotoxaemia and in the in vitro stimulated PBMCs. A low steady expression of TLR4, MD-2 and CD14 mRNA was demonstrated for the intestinal samples with no variation between the intestinal segments analysed. Thus, the foundation for real time PCR based levels of analysis of mRNA for all three components in the equine LPS receptor complex in different intestinal segments was set, making it possible to carry out future expression studies on clinical material.

Keywords
Equine, tlr4, md2, cd14, Intestine, Endotoxin, qPCR
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-191026 (URN)10.1016/j.vetimm.2012.09.005 (DOI)000312052500001 ()
Available from: 2013-01-10 Created: 2013-01-09 Last updated: 2017-12-06Bibliographically approved
Yu, Q., Shuai, H., Ahooghalandari, P., Gylfe, E. & Tengholm, A. Glucose controls glucagon secretion by directly modulating cAMP in α‑cells.
Open this publication in new window or tab >>Glucose controls glucagon secretion by directly modulating cAMP in α‑cells
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(English)In: Article in journal (Other (popular science, discussion, etc.)) Submitted
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-356473 (URN)
Available from: 2018-07-29 Created: 2018-07-29 Last updated: 2018-07-31
Yu, Q., Lai, B. K., Ahooghalandari, P., Helander, A., Gylfe, E., Gilon, P. & Tengholm, A.γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion.
Open this publication in new window or tab >>γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion
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(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-356475 (URN)
Available from: 2018-07-29 Created: 2018-07-29 Last updated: 2018-07-31
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