Perinatal Taurine Imbalance Alters the Interplay of Renin–Angiotensin System and Estrogen on Glucose–Insulin Regulation in Adult Female Rats - Advances in Experimental Medicine and Biology - page 74

that the combination of perinatal taurine depletion followed by high sugar intake
after weaning amplifies the beneficial chronic effects of RAS on glucose-insulin
regulation. In this case, RAS affects both insulin sensitivity and insulin secretion,
thus protecting the rats from hyperglycemia and glucose intolerance.
We previously reported that perinatal taurine depletion slightly and significantly
blunts baroreceptor reflex sensitivity of heart rate in adult female rats, and this effect
was exacerbated by high sugar intake after weaning (Roysommuti et al. 2009a ) .
Acute inhibition of RAS by captopril completely abolishes sugar-induced baroreflex
dysregulation and sympathetic nerve overactivity, suggesting that the RAS overac-
tivity underlies these effects (Thaeomor et al. 2010 ). In contrast, in the present study,
a similar RAS inhibition worsened insulin resistance in TDG rats. These data imply
that RAS-mediated changes in baroreflex and/or sympathetic nerve overactivity
may not contribute to insulin resistance in perinatal taurine-depleted rats. These
findings together suggest that the effects of RAS on glucose-insulin regulation may
be age (or time post taurine exposure) sensitive.
Angiotensin II can decrease insulin secretion by directly binding to AT 1 recep-
tors on beta cells. Further, angiotensin II may act in conjunction with an aldoster-
one-receptor complex and alters cell glucose metabolism, ATP-sensitive potassium
channels, glucose transporter translocation, and insulin granule exocytosis (Luther
and Brown 2011 ). Recent evidence indicates that pancreatic islet cells contain
local RAS that can generate both angiotensin II and angiotensin (1-7). While both
local and systemic angiotensin II have similar actions on beta cells, angiotensin
(1-7) acts on AT 1-7 receptor, typically antagonizing angiotensin II's action (Cheng
and Leung 2011 ; Hayden et al. 2011 ). Other than its hemodynamic action, chronic
angiotensin II can induce insulin resistance by acting on AT 1 receptors on insulin-
sensitive cells, increasing oxidative stress, and disturbing several cellular mediators
of glucose uptake (Luther and Brown 2011 ) .
Perinatal taurine supplementation is commonly taken by pregnant and lactating
women and given to newborn children as supplements. Although adverse effects of
taurine excess have not been definitively demonstrated in humans, taurine supple-
mentation in late pregnant rats stimulates postnatal growth and induces obesity and
insulin resistance in 12-week-old offspring (Hultman et al. 2007 ) . The present study
demonstrates that perinatal taurine supplementation without high sugar intake after
weaning does not alter body weight, insulin secretion, insulin sensitivity, and glu-
cose tolerance in adult offspring (TSW), and that the actions of RAS and estrogen
on glucose-insulin regulation are preserved in these rats. However, when the
taurine-supplemented rats are placed on a high sugar diet after weaning (TSG),
these parameters are slightly impaired, but remain much better than those of TDG
rats. While 7-8-week-old TSG rats do not display insulin resistance severe enough
to produce hyperglycemia and glucose intolerance, the effect may amplify with
advancing age, as previously reported (Hultman et al. 2007 ) .
The incidence of diabetes mellitus and cardiovascular diseases increases in
menopausal women and hormonal therapy can prevent or improve these abnor-
malities (Kim 2012 ; Meyer et al. 2011 ; Kim 2012 ; Meyer et al. 2011 ) . Estrogen
plays a key role in fat distribution and energy expenditure in females. Thus, estrogen