title: Protein phosphatases in pancreatic islets.
abstract: The prevalence of diabetes is increasing rapidly worldwide. A cardinal feature of most forms of diabetes is the lack of insulin-producing capability, due to the loss of insulin-producing β-cells, impaired glucose-sensitive insulin secretion from the β-cell, or a combination thereof, the reasons for which largely remain elusive. Reversible phosphorylation is an important and versatile mechanism for regulating the biological activity of many intracellular proteins, which, in turn, controls a variety of cellular functions. For instance, significant changes in protein kinase activities and in protein phosphorylation patterns occur subsequent to the stimulation of insulin release by glucose. Therefore, the molecular mechanisms regulating the phosphorylation of proteins involved in the insulin secretory process by the β-cell have been extensively investigated. However, far less is known about the role and regulation of protein dephosphorylation by various protein phosphatases. Herein, we review extant data implicating serine/threonine and tyrosine phosphatases in various aspects of healthy and diabetic islet biology, ranging from control of hormonal stimulus-secretion coupling to mitogenesis and apoptosis.
authors.affiliation: Biovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, SwedenBiovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ortsäter
authors.affiliation: Biovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Grankvist
authors.affiliation: Biovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, Sweden.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Honkanen
authors.affiliation: Biovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, SwedenBiovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, SwedenBiovation Park TelgeSödertälje, SwedenResearch UnitSödertälje Hospital, SE-152 86 Södertälje, SwedenDegenerative Disease ProgramSanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, 10901 North Torrey Pines Road, La Jolla, California 92037, USADepartment of Biochemistry and Molecular BiologyCollege of Medicine, University of South Alabama, Mobile, Alabama 36688, USADepartment of Internal MedicineSödertälje Hospital, Södertälje, Sweden ake.sjoholm@sodertaljesjukhus.se.
authors.forename: Åke
authors.initials: Å
authors.lastname: Sjöholm
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000145:classification / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D007328:Insulin; D010750:Phosphoproteins; D010749:Phosphoprotein Phosphatases; D005947:Glucose
keywords: apoptosis; diabetes; insulin secretion; islet cells; phosphatase