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receptor alpha knockout mice display increased adipose tissue, increased weight,
insulin resistance, impaired glucose tolerance, hyperglycemia, and decreased
energy expenditure (Heine et al.
2000
). The present study indicates that estrogen
plays a very minor role on glucose-insulin regulation in young adult female rats
that receive normal or excess taurine during the perinatal period. In contrast,
in rats receiving perinatal taurine depletion followed by the high sugar intake
after weaning, estrogen plays a relatively important role in preventing hypergly-
cemia and glucose intolerance. This very specific effect of estrogen is only seen
in the TD group on a high sugar diet. Several lines of evidence indicate that
estrogen may directly or indirectly inhibit RAS and sympathetic nervous system
(Ashraf and Vongpatanasin
2006
); however, inhibition of the RAS in the TD group
inhibits the sympathetic nervous system (Thaeomor et al.
2010
) and increases
both insulin secretion and insulin resistance without hyperglycemia and glucose
intolerance.
We reported previously that the high sugar intake (similar to the present proto-
col) induces renal dysfunction before hyperglycemia and glucose intolerance, an
effect that is reversed by captopril treatment (Roysommuti et al.
2002
) . In rats
receiving normal perinatal taurine, high sugar intake after weaning abolishes the
effect of RAS inhibition on insulin resistance and insulin secretion, a situation not
observed in other groups. While the mechanism underlying this phenomenon can-
not presently be resolved, this suggests that perinatal taurine exposure alters RAS in
response to a high sugar diet in the adult.
8.5
Conclusion
In summary, perinatal taurine exposure affects adult glucose-insulin regulation and
affects the RAS and estrogen regulation of glucose/insulin homeostasis. This effect
may involve epigenetic programming of RAS and estrogen function, a phenomenon
that can be altered or amplified by a high sugar diet after weaning. While both peri-
natal taurine excess and depletion can alter the effects of RAS and estrogen on
glucose-insulin regulation, perinatal taurine depletion appears to have a much
greater effect. Further, in contrast to the chronic effects of RAS and estrogen inhibi-
tion, short-term RAS and estrogen inhibition cause rather different responses. The
short-term responses found in this study suggest that endogenous estrogen protects
against glucose intolerance, while endogenous RAS protects against insulin resis-
tance. How these effects relate to the effects of long-term treatment with RAS or
estrogen blockers remains to be determined.
Acknowledgements
This study was supported by a grant from the Faculty of Medicine, Khon
Kaen University, Khon Kaen 40002, Thailand, and by the US National Institutes of Health (NIH)
grants AT 00477 and NS057098 (JMW).
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