title: Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations.
abstract: In healthy humans, insulin is secreted in an oscillatory manner. While the underlying mechanisms generating these oscillations are not fully established, increasing evidence suggests a central role for phosphofructo-1-kinase/muscle subtype (PFK1-M), which also serves as the predominantly active PFK1 subtype in the pancreatic beta-cell. The fact that normal oscillatory secretion is impaired in subjects with impaired glucose tolerance and healthy relatives of patients with type 2 diabetes suggests that this defect may be involved in the secretory dysfunction. To evaluate a possible link between inherited PFK1-M deficiency in humans (Tarui's disease or glycogenosis type VII) and altered insulin oscillations, in vivo studies were performed. We determined basal insulin oscillations during 2 h of frequent plasma sampling in two related teen-aged individuals with homozygous and heterozygous PFK1-M deficiency compared with nondeficient, unrelated control subjects. As predicted by the underlying hypothesis, normal oscillations in insulin secretion were completely abolished in the individual with homozygous deficiency of PFK1-M and significantly impaired in the heterozygous individual, as shown by spectral density and autocorrelation analyses. Thus, deficiency of PFK1-M subtype in humans appears to be associated with an impaired oscillatory insulin secretion pattern and may contribute to the commonly observed secretion defects occurring in type 2 diabetes.
authors.affiliation: Klinik II und Poliklinik für Innere Medizin, Universität zu Köln, Cologne, Germany. michael.ristow@uni-koeln.de
authors.forename: M
authors.initials: M
authors.lastname: Ristow
authors.forename: H
authors.initials: H
authors.lastname: Carlqvist
authors.forename: J
authors.initials: J
authors.lastname: Hebinck
authors.forename: M
authors.initials: M
authors.lastname: Vorgerd
authors.forename: W
authors.initials: W
authors.lastname: Krone
authors.forename: A
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: D
authors.initials: D
authors.lastname: Müller-Wieland
authors.forename: C G
authors.initials: CG
authors.lastname: Ostenson
mesh_terms: D000328:Adult; D002648:Child; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009132:Muscles / Q000201:enzymology*; D009991:Oscillometry; D010732:Phosphofructokinase-1 / Q000172:deficiency*; D012016:Reference Values
chemical_list: D007328:Insulin; D010732:Phosphofructokinase-1; C068652:1-phosphofructokinase