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Absence of renal enlargement in fructose-fed proximal-tubule-select insulin
receptor (IR), insulin-like-growth factor receptor (IGF1R) double knockout mice
#MMPMID27923977
Li L
; Byrd M
; Doh K
; Dixon PD
; Lee H
; Tiwari S
; Ecelbarger CM
Physiol Rep
2016[Dec]; 4
(23
): ? PMID27923977
show ga
The major site of fructose metabolism in the kidney is the proximal tubule (PT).
To test whether insulin and/or IGF1 signaling in the PT is involved in renal
structural/functional responses to dietary fructose, we bred mice with dual
knockout (KO) of the insulin receptor (IR) and the IGF1 receptor (IGF1R) in PT by
Cre-lox recombination, using a ?-glutamyl transferase promoter. KO mice had
slightly (~10%) reduced body and kidney weights, as well as, a reduction in mean
protein-to-DNA ratio in kidney cortex suggesting smaller cell size. Under control
diet, IR and IGF1R protein band densities were 30-50% (P < 0.05) lower than WT,
and the relative difference was greater in male animals. Male, but not female KO,
also had significantly reduced band densities for Akt (protein kinase B),
phosphorylated Akt(T308) and IR(Y)(1162/1163) A high-fructose diet (1-month) led
to a significant increase in kidney weight in WT males (12%), but not in KO males
or in either genotype of female mice. Kidney enlargement in the WT males was
accompanied by a small, insignificant fall in protein-to-DNA ratio, supporting
hyperplasia rather than hypertrophy. Fructose feeding of male WT mice led to
significantly higher sodium bicarbonate exchanger (NBCe1), sodium hydrogen
exchanger (NHE3), sodium phosphate co-transporter (NaPi-2), and transforming
growth factor-? (TGF-?) abundances, as compared to male KO, suggesting elevated
transport capacity and an early feature of fibrosis may have accompanied the
renal enlargement. Overall, IR and/or IGF1R appear to have a role in PT cell size
and enlargement in response to high-fructose diet.
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