Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

metabolite of leucine, alpha-ketoisocaproic acid (KIC) was

unable to stimulate lipolytic activation. Leucine exposure

results in phosphorylation of mTOR in adipocytes. However,

blocking mTOR activation with rapamycin had no effect on

leucine-mediated stimulation of lipolysis. Efforts are under-

way to determine the site of action for leucine-stimulation of

lipolysis in cultured adipocytes. The novel finding that leucine

can sensitize adipocytes to lipolytic activation provides a

possible explanation for the link between elevated circulating

leucine levels and the development of insulin resistance.

Reference

Newgard C.B., Interplay between lipids and branched-chain

amino acids in development of insulin resistance.

Cell Metab

2012. 15(5): 606

–

14.

PH-12

Impaired RBC deformability is associated with pancreatic beta

cell dysfunction and diabetic retinopathy in patients with type

2 diabetes

Ho Jin KIM

*, Jun Sung MOON

, Ji Sung YOON

Kyu Chang WON

, Hyoung Woo LEE

Department of Internal

Medicine, Yeungnam University College of Medicine, Korea

Aim:

Red blood cell (RBC) deformability is an ability of RBC to

change shape under stress, and it has been known to be

decreased in diabetes. However, the role of RBC deformability

is not determined in type 2 diabetes (T2D) yet. We attempted to

clarify whether RBC deformability is related with diabetic

complications.

Methods:

This was a cross-sectional study, and 452 T2D

patients were enrolled. RBC deformability was measured by

using a microfluidic ektacytometer and expressed as elong-

ation index at 3 Pa (EI@3P, %).

Results:

388 patients (mean age 60.37 ± 11.98 years, male 233)

were finally included. When subjects were categorized into

three groups by hemoglobin A1c (HbA1c; <7% vs. 7

≤

<9% vs.

≥

9%), mean EI@3 Pa was significantly lower in the poorly

controlled group (31.23 ± 1.60 vs 31.00 ± 1.82 vs. 30.70 ± 1.64,

p < 0.05 by ANOVA). HOMA-B and insulinogenic index were

positively correlated with EI@3 Pa but not with HOMA-IR in

multiple regression analysis. EI@3 Pa was significantly lower

only in patients with retinopathy than those without retinop-

athy (30.53 ± 1.95 vs. 31.20 ± 1.53, p = 0.001). Of quartiles from

lowest EI@3 Pa to highest (reference), the odds ratio (OR) for Q1

was 2.86 (95% confidence interval 1.24, 6.62, p = 0.014) after

adjustment for age, gender, hypertension, smoking, duration

of diabetes, GFR, and triglyceride. If EI@3 Pa increase by 1%, the

risk of diabetic retinopathy will decrease by 24.9%.

Conclusions:

These results suggest that impaired RBC deform-

ability is related with decreased pancreatic beta cell function

and the risk of diabetic retinopathy.

PH-13

Inhibition of RAC1-NOX signaling attenuates high-glucose-

induced CD36 expression in pancreatic

-cells

Jun Sung MOON

, Ho Jin KIM

, Ji Sung YOON

Hyoung Woo LEE

, Kyu Chang WON

Department of Internal

Medicine, Yeungnam University College of Medicine, Korea

Objective:

Cluster determinant 36 (CD36), a fatty acid trans-

porter, was reported to have a pivotal role in glucotoxicity-

induced

-cell dysfunction. However, little is known about how

glucotoxicity influences CD36 expression. So, the predominant

objective is to reveal the role of RAC1-NOX in CD36 activation

and its impact for the

-cell dysfunction during diabetes

mellitus.

Methods:

To address this question, we subjected INS-cells

and primary rat islets to high glucose (30 mM) for 24 hours

in the absence or presence of RAC1 inhibitor NSC23766.

Apoptosis was measured by TUNEL-Nick End Labeling

assay. RAC1 and NOX activity was assessed using the Rac1

Activation Assay kit (Merck Millipore)

and by

chemiluminescenceassay. Reactive oxygen species and mito-

chondrial membrane potential were measured by using

DCFDA and DIOC6 dye respectively. Moreover, the protein

expression level of CD36, MAPK signaling pathways in

response to high glucose is assessed by western blot analysis.

Results:

Exposure of INS-1 cells to high glucose (30 mM)

upregulated RAC1 and NADPHoxidase activation, and

induced apoptosis. Interestingly, upregulated RAC1 and

NADPH oxidase induced CD36 expression. These effects of

high glucose were significantlydecreased in INS-1 cells treated

with NSC23766. Moreover, RAC1 inhibition by NSC23766

significantly reduced high glucose-induced mitochondrial

dysfunction assessed by measuring the mitochondrial mem-

brane potential and cytochrome c release. Inhibition of RAC1

also attenuated MAPK signaling.

Conclusion:

RAC1 regulates NOX activity, thereby increasing

the expression of CD36 and its downstream signaling lead to

cell dysfunction under high glucose conditions.

PH-14

A comparison of sympathetic and parasympathetic nerves

density ratio in pancreatic islets in experimental animal model

Hyun Ah KO

, Yu Ji KIM

1,2

, Kyung Ae LEE

1,2

, Heung Yong JIN

1,2

Hong Sun BAEK

1,2

, Tae Sun PARK

1,2

Chonbuk National

University Medical School Endocrinology and Metabolism,

Chonbuk

National University Hospital Research Institute of Clinical Medicine,

Korea

Purpose:

The change of sympathetic and parasympathetic

nerves ratio in pancreatic islets have been unclear during

diabetes progression. A connection and an insulin secretion of

sympathetic and parasympathetic nerves in pancreatic islet

are studied on the area of innervated sympathetic, parasym-

pathetic nerves in normal and diabetes rat.

Method:

The pancreas of normal and diabetes induced

Sprague

–

Dawley (SD) rats (n = 4

–

5/group) were fixed by forma-

lin and were dehydrated by sucrose. After cut by freezing

microtome into 40

m thick sections, the tissues were stained

with protein gene product 9.5, tyrosine hydroxylase and

choline acetyltransferase for islet cell, sympathetic and para-

sympathetic nerves. All of the stained sections were imaged

by confocal microscopy and the images were analyzed to area

of sympathetic and parasympathetic nerves by pixel and

calculated the ratio of parasympathetic to sympathetic ratio.

Result:

There was no significant difference in the area of

parasympathetic nerves between normal and diabetic rat

pancreatic islets, but the area of sympathetic nerve of diabetic

rat was much higher than normal in pancreatic islet. The

parasympathetic to sympathetic nerve density ratio of diabetic

rat was smaller than normal control rats (9.84 vs 40.3).

Conclusion:

This study is demonstrated that parasympathetic

to sympathetic nerve density ratio markedly decreased in

diabetic animal model.

PH-15

Sympathetic to parasympathetic nerve density ratio change in

adipocytes in diabetic animal models

NaYoung LEE

, Hyun Ah KO

, Yu Ji KIM

, Kyung Ae LEE

Heung Yong JIN

1,2

, Hong Sun BAEK

1,2

, Tae Sun PARK

1,2

Chonbuk National University Medical School Research institute of

Clinical Medicine,

Chonbuk National University Hospital

Endocrinology and Metabolism, Korea

Background:

White adipose tissue in relation with lipid

mobilization is innervated by sympathetic peripheral nerve

and lipid metabolism is also important in peripheral nerve

regeneration. Autonomic neuropathy involving these sympa-

thetic and parasympathetic nerves is an important and

common chronic complication in diabetes and adipocyte is

also important for metabolic parameters in diabetes. However,

there is no research about the relation between adipose

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