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.
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Authors | M Ristow, H Carlqvist, J Hebinck, M Vorgerd, W Krone, A Pfeiffer, D Müller-Wieland, C G Ostenson |
Journal | Diabetes
(Diabetes)
Vol. 48
Issue 8
Pg. 1557-61
(Aug 1999)
ISSN: 0012-1797 [Print] United States |
PMID | 10426373
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Insulin
- Phosphofructokinase-1
- 1-phosphofructokinase
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Topics |
- Adult
- Child
- Heterozygote
- Homozygote
- Humans
- Insulin
(metabolism)
- Insulin Secretion
- Male
- Muscles
(enzymology)
- Oscillometry
- Phosphofructokinase-1
(deficiency)
- Reference Values
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