Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate
- PMID: 6344863
- PMCID: PMC1154224
- DOI: 10.1042/bj2100297
Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate
Abstract
The concentrations of Zn2+, Ca2+, Mg2+, Pi and adenine nucleotides were determined in insulin-secretory granules prepared from a transplantable rat insulinoma. Differential and density-gradient centrifugation analyses revealed that Zn2+ in this tissue was principally localized in the secretory granule, a second major fraction being found in association with cytosolic proteins. Pi was principally recovered in the latter fraction, whereas Ca2+ and Mg2+ were more widely distributed. Intragranular ion-distribution experiments suggested that Zn2+ was complexed mainly to insulin and its precursor forms and remained in the granule in an insoluble state. The Zn2+/insulin ratio (0.54) was greater than that expected for insulin molecules having two centrally co-ordinated Zn2+ atoms/hexamer, but less than the maximal Zn2+-binding capacity of the molecule. Most of the granular Ca2+, Mg2+ and Pi was released in a soluble form when granules were disrupted by sonication. Simulation in vitro of the ionic composition of the granule suggested that up to 90% of its Ca2+ was complexed to Pi and adenine nucleotides. Granular macromolecules also bound Ca2+, as shown by equilibrium-dialysis studies of granule lysates. However, such binding was displaced by Mg2+. Examination of the efflux of Ca2+ from granules incubated in iso-osmotic suspensions at 37 degrees C suggested that the passive permeability of the granule membrane to Ca2+ was very low. Nevertheless, more than 50% of the granular Ca2+ was rapidly released in an ionized form on hypo-osmotic or detergent-induced disruption of the granule membrane. This may represent a potentially mobilizable pool of Ca2+ in vivo.
Similar articles
-
Nucleotide and bivalent cation specificity of the insulin-granule proton translocase.Biochem J. 1983 Jan 15;210(1):235-42. doi: 10.1042/bj2100235. Biochem J. 1983. PMID: 6303313 Free PMC article.
-
5-Hydroxytryptamine transport in cells and secretory granules from a transplantable rat insulinoma.Biochem J. 1983 Mar 15;210(3):803-10. doi: 10.1042/bj2100803. Biochem J. 1983. PMID: 6307272 Free PMC article.
-
Regulation of Ca2+ transport by isolated organelles of a rat insulinoma. Studies with endoplasmic reticulum and secretory granules.J Biol Chem. 1984 Aug 25;259(16):10118-23. J Biol Chem. 1984. PMID: 6088482
-
Phylogenetic considerations of neurosecretory granule contents: role of nucleotides and basic hormone/transmitter packaging mechanisms.Arch Histol Cytol. 1989;52 Suppl:277-92. doi: 10.1679/aohc.52.suppl_277. Arch Histol Cytol. 1989. PMID: 2573383 Review.
-
The endocrine secretion granule revisited- postulating new functions.Metabolism. 1982 Sep;31(9):959-67. doi: 10.1016/0026-0495(82)90189-5. Metabolism. 1982. PMID: 6126795 Review. No abstract available.
Cited by
-
Recent advances in understanding the extracellular calcium-sensing receptor.F1000Res. 2016 Oct 19;5:F1000 Faculty Rev-2535. doi: 10.12688/f1000research.8963.1. eCollection 2016. F1000Res. 2016. PMID: 27803801 Free PMC article. Review.
-
The enzymology of proinsulin conversion.Cell Biophys. 1991 Oct-Dec;19(1-3):57-62. doi: 10.1007/BF02989879. Cell Biophys. 1991. PMID: 1726888 Review. No abstract available.
-
Production and characterization of monoclonal antibodies to insulin secretory granule membranes.Biochem J. 1987 Jul 15;245(2):557-66. doi: 10.1042/bj2450557. Biochem J. 1987. PMID: 2444218 Free PMC article.
-
Insulin granule dynamics in pancreatic beta cells.Diabetologia. 2003 Aug;46(8):1029-45. doi: 10.1007/s00125-003-1153-1. Epub 2003 Jul 17. Diabetologia. 2003. PMID: 12879249 Review.
-
The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus.Antioxid Redox Signal. 2017 Apr 1;26(10):501-518. doi: 10.1089/ars.2016.6755. Epub 2016 Jun 30. Antioxid Redox Signal. 2017. PMID: 27225690 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous