Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

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transcription of TCF-responsive genes. The effect of feeding
was mimiced by specific metabolic hormones, including GLP1
and insulin. Finally, experimental modification of β-catenin
levels in a hypothalamic cell line altered neuropeptide
secretion. The data suggest that both transcriptional and
non-transcriptional effects of β-catenin in the hypothalamus
might be involved in the regulation of body weight and glucose
homeostasis, and highlights the potential role of altered
hypothalamic function in contributing to the risk of diabetes
conferred by specific genetic polymorphisms of TCF7L2 in
human populations.
S38-2
Insulin signaling in adipocytes and metabolic control
Wataru OGAWA 1, Tetsuya HOSOOKA1, Masato KASUGA2.
1 Division of Diabetes and Endocrinology, Kobe University Graduate
School of Medicine, Kobe, 2National Center for Global Health and
Medicine, Tokyo, Japan
Insulin signaling in adipocyte is thought to play a key role in
the control of energy metabolism in living animals. The
pathophysiological significance of insulin resistance in adipo-
cyte remains ambiguous, however. To understand the physio-
logical impact of insulin resistance in adipocytes in living
animals, we have generatedmice lacking PDK1, a keymolecule
in insulin signaling, selectively in adipocytes. Insulin-induced
biological actions in adipose tissue, including the stimulation
of glucose uptake and lipogenesis as well as the inhibition of
lipolysis, were almost completely prevented in adipocyte-
specific PDK1 deficient mice (A-PDK1KO mice). The mass of
adipose tissue as well as the plasma levels of adiponectin
and leptin were decreased in A-PDK1KO mice. A-PDK1KO mice
manifest severe insulin resistance, glucose intolerance,
and dyslipidemia under normal chow feeding. Moreover,
A-PDK1KO mice naturally develop nonalcoholic steatohepati-
tis (NASH) within ∼ 35 weeks of age. A transcription factor
FoxO1 is a negative regulator of insulin action. Insulin-induced
phosphorylation of FoxO1 was abolished in the adipose tissue
of A-PDK1KO mice, indicating that the FoxO1-dependent
pathway is constantly activated. To investigate whether the
activation of the FoxO1 pathway contributes to the meta-
bolic abnormalities of A-PDK1KO mice, we have additionally
disrupted FoxO1 selectively in adipocytes in A-PDK1KO mice.
The additional disruption of FoxO1 markedly ameliorated
metabolic abnormalities in A-PDK1KO mice including insulin
resistance, glucose intolerance and NASH without affecting
the mass of adipose tissue, the plasma levels of the adipo-
nectin and leptin. Our results suggest that the impairment
of insulin action in adipocytes contributes not only to the
pathogenesis of insulin resistance and glucose intolerance, but
also to that of NASH. Furthermore, the FoxO1-dependent
transcriptional pathway appears to be greatly attributable
to these pathological conditions. Further analysis of the PDK1-
FoxO1 pathway in adipocytes may shed light on the patho-
genesis of NASH and may lead to the development of a novel
therapeutic approach for this global health problem.
S38-4
Role of mitochondrial quality control in hyperglycemic
neuroprotection
Daniel HESSELSON 1. 1Garvan Institute of Medical Research,
Sydney, Australia
Population based studies have identified a link between
Diabetes mellitus (DM) and the risk of developing Parkinson ’s
disease (PD). The duration of prior DM has emerged as an
independent risk factor for PD suggesting that dopaminergic
neurons are susceptible to repeated hyperglycemic insults.
Recent large-scale studies in the Taiwanese population
have strengthened this association and further suggested
that selected oral anti-hyperglycemic agents offer partial
protection. However, the molecular mechanisms underlying
DM-associated PD risk remain unclear. One possibility is that
both diseases share common genetic and environmental risk
factors. Alternatively, exposure to hyperglycemic conditions
may trigger neurodegeneration in susceptible individuals. We
have developed cell and animal (zebrafish) models to investi-
gate the role of PD-associated mitochondrial quality control
pathways in the neuronal response to hyperglycemia using
unbiased proteomic approaches. As the repertoire of anti-
hyperglycemic agents expands it will be essential to identify
which drugs offer additional neuroprotective benefit to aging
populations.
Nutrition and Exercise in Diabetes
S19-2
Alternative health eating index and the Dietary Guidelines
from American Diabetes Association both may reduce the risk
of cardiovascular disease in type 2 diabetes patients
Sherry Shwu-Huey YANG1. 1School of Nutrition and Health
Science, Taipei Medical University, Taipei, Taiwan
Type 2 diabetes mellitus (T2DM) is associated with an
increased risk of cardiovascular disease (CVD) and is consid-
ered to represent a primary risk factor for coronary heart
disease (CHD). Diet is crucial for disease prevention and
treatment, and the risk of chronic disease is more highly
correlated with overall diet than with a single nutrient. In
the general population, healthy dietary patterns have been
documented as reducing CVD risk. The Alternate Healthy
Eating Index (AHEI), developed on the basis of the Dietary
Guidelines for Americans, is designed to reduce chronic
disease risk. In 2012, Chiuve et al. released AHEI-2010,
an updated version of the index that includes additional
dietary suggestions for reducing risk of chronic disease, such
as consuming legumes and avoiding sugar-sweetened bev-
erages. A higher AHEI-2010 score has been demonstrated to
predict a 27–44% lower cardiovascular disease (CVD) mortality
in the general Chinese population. The American Diabetes
Association (ADA) have provided dietary recommendations
to enable patients with DM to reduce their risk of CHD.
We developed an ADA dietary score according to the ADA
dietary recommendations. The ADA dietary score contained 10
components, namely seven adequate components and three
moderate components. The total ADA dietary score was the
sum of the scores for the 10 components. A score of 0 or 1 was
assigned for the components: (i) proportion of whole grains; (ii)
vegetables; (iii) fruit; (iv) low-fat dairy; (v) protein foods; (vi)
seafood and plant protein; (vii) fatty acids ratio; oils; (ix) empty
energy; and (x) sodium. The AHEI-2010 scores are calculated
and detailed descriptions provided in the Chiuve’s (2012)
literature. In brief, a higher AHEI-2010 score indicates a higher
intake of vegetables, fruit, whole grains, nuts and legumes,
polyunsaturated fatty acids (PUFA) and long-chain (n-3) fats, in
addition to a moderate intake of sugar-sweetened beverages
and fruit juice, processed meat, sodium, trans fat and alcohol.
The AHEI-2010 scores range from 0 to 110. A prospective study,
the 24-h dietary recall of 124 adult T2DM patients without
nephropathy or chronic kidney disease was conducted. The
CVD risk factors were collected at baseline and at 6-month
follow-up. Compared with lower ADA and AHEI-2010 score
participants, the higher score participants exhibited a signi-
ficantly lower waist circumference, serum low-density lipo-
protein cholesterol level and 10-year risk of CHD. Participants
with higher ADA dietary scores had a significantly reduced risk
of central obesity and systolic blood pressure >140 mmHg.
Higher AHEI-2010 scores were significantly related to a
reduced risk of serum low-density lipoprotein cholesterol
Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1–S39 S27