In:
Diabetes, American Diabetes Association, Vol. 59, No. 8 ( 2010-08-01), p. 1957-1965
Abstract:
It is believed that an organism remains normoglycemic despite an increase in the β-cell mass because of decreased insulin production by β-cells on a per-cell basis. However, some transgenic mouse models with β-cell hyperplasia suggest that insulin production remains excessive and that normoglycemia is maintained by insulin resistance. METHODS Here, we investigated the effect of an increased β-cell mass on glycemia and insulin resistance by grafting excess normal islets in normoglycemic mice, as well as using targeted PLAG1 expression in β-cells, which leads to β-cell expansion. RESULTS In both models, fasting plasma insulin levels were increased, even though animals were normoglycemic. After an intraperitoneal glucose tolerance test, plasma insulin levels increased, which was associated with improved glucose clearing. Under these conditions, normoglycemia is maintained by hepatic insulin resistance as demonstrated by hyperinsulinemic euglycemic clamp experiments. CONCLUSIONS In conclusion, we demonstrate that when excess β-cells are grafted, insulin production on a per β-cell basis is not sufficiently decreased, leading to hyperinsulinemia and hepatic insulin resistance. This observation might be important for the design of stem cell-based islet replacement therapies.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2010
detail.hit.zdb_id:
1501252-9
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