Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations.
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.
Ristow
M
M
Klinik II und Poliklinik für Innere Medizin, Universität zu Köln, Cologne, Germany. michael.ristow@uni-koeln.de
Carlqvist
H
H
Hebinck
J
J
Vorgerd
M
M
Krone
W
W
Pfeiffer
A
A
Müller-Wieland
D
D
Ostenson
C G
CG
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
D007328:Insulin; D010732:Phosphofructokinase-1; C068652:1-phosphofructokinase