Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Background:

Cytomegalovirus (CMV) is readily transmitted

from seropositive solid organ donors to CMV seronegative

recipients (CMV-mismatch) despite the use of antiviral

prophylaxis and can cause highly morbid and even fatal

illness. Type 1 diabetic patients are known to have reduced

odds of CMV seropositivity when compared with potential

donors. Therefore, the proportion of transplant recipient who

has CMV-mismatch in islet cases is significantly higher than

that in solid organ transplant (SOT). Our previous study has

shown that there is a lower rate of CMV transmission in islet

transplant recipients. It is unclear if the recent modification of

islet transplant induction protocol has an impact on the rate of

transmission.

Methods:

Our study was an observational retrospective study

comparing the rate of transmission of CMV, in CMV mis-

matched islet transplant recipients (n = 45) to a control group

of CMV mismatched SOT recipients (n = 27) corresponding to

the same donor at the University of Alberta Hospital from

March 1999 to May 2014.

Results:

CMVmismatched islet transplant recipients were less

likely to have CMV transmission (8.9%) than CMV mismatched

SOT recipients (78%) despite receiving tissues from the same

donors. CMV transmission rates in islet transplant had

increased due to the recent modification of induction protocol.

Conclusions:

Low number of contaminating leukocytes due

to stringent retrieval and purification process of islet, the

success of immunosuppression protocols in maintaining

low rejection rate along with low cytokine response which

might promote CMV reactivation and the lack of surgical

procedure which might lead to pro-inflammatory state that

reactivates CMV in recipients are the postulated reasons for

the lower transmission rate in islet transplant cases. The

recent intensification of islet transplant induction protocol

which renders islet recipients more immunosuppressed than

before might have contributed to the higher rate of CMV

transmission in this current cohort than the one from our

previous study.

PH-04

Identifying a new pathway to regulate AMPK activity under

metabolic stress

Eijiro YAMADA

*, Shuichi OKADA

, Ryo SHIBUSAWA

Yuko TAGAYA

, Aya OSAKI

, Yoko SHIMODA

Tsugumichi SAITO

, Claire BASTIE

, Jeffrey PESSIN

Masanobu YAMADA

Department of Medicine and Molecular

Science, Gunma University Graduate School of Medicine, Mabashi,

Japan;

Department of Medicine, Albert Einstein College of Medicine,

Bronx, NY, United States of America

Metabolic stress is associated with diabetes and insulin

resistance and these patho-physiologies are linked with

dysfunctions of nutrient-sensors such as AMP-dependent

protein kinase (AMPK). Additionally pro-inflammatory cyto-

kines such as TNF

secreted from adipose tissue contributes to

chronic low-grade inflammation and whole body insulin

resistance. Previously we reported that Fyn knull mice

display increased energy expenditure and fatty acid oxidation

due to increased AMPK activity in peripheral tissues. More

recently, we demonstrated that Fyn regulates AMPK activity

not only indirectly via its action on LKB1, but also by direct

modulation of AMPK activity through Y426 phosphorylation

of the

subunit. To investigate how Fyn regulates AMPK

activity, we made AMPK

-Y426F mutant and examine

functional interactions of the

subunit with the

and

subunits. Although co-immunoprecipitation demonstrated no

significant difference in

and

subunit binding, the

-Y426F

mutant displayed increased kinase activity compared to the

wild type

subunit. These data suggested that Fyn-dependent

tyrosine phosphorylation of AMPK

subunit on Y426 regulates

its intra-molecular activity.

To assess this pathway has a critical role under metabolic

disease, we further investigated the signaling crosstalk

between Fyn and pro-inflammatory cytokines, TNF

AMPK regulation. Time course analyses revealed that acute

treatment with TNF

(10 ng/mL for 12 h) enhanced AICAR

(2 mM, 10 min) dependent phosphorylation of the AMPK

subunit on the activation T172 site. In contrast, prolonged

incubation with TNF

(24

–

36 hr) suppressed AICAR stimulated

T172

subunit phosphorylation. In parallel, TNF

increased

Fyn tyrosine kinase activity and siRNA knockdown of Fyn

prevented the chronic TNFa inhibition of AICAR-stimulated

AMPK T172

subunit phosphorylation. Taken together,

these data suggest that prolonged stimulation of TNF

blunts

AICAR dependent AMPK activation through Fyn-dependent

tyrosine phosphorylation of AMPK

subunit.

PH-05

High molecular weight adiponectin and lipid profile in the

type-2 diabetes mellitus-Mets

Deasy ARDIANY

*, Askandar TJOKROPRAWIRO

Ari SUTJAHJO

, Agung PRANOTO

, Sri MURTIWI

Soebagijo ADI

, Sony WIBISONO

Surabaya Diabetes and

Nutrition Centre - Dr. Soetomo Teaching Hospital Faculty of Medicine

Airlangga University, Surabaya, Indonesia

Background:

Dyslipidemia is a major component of the

metabolic syndrome (Mets) and a strong risk factor for the

development of cardiovascular disease. High Molecular

Weight (HMW) Adiponectin is an adipocyte-derived hormone

that enhances insulin sensitivity. It plays an important role in

glucose and lipid metabolism. Plasma HMW adiponectin level

is decreased in patients with type 2 diabetes. The effects of

dyslipidemia on plasma HMW adiponectin levels in human

subjects have not yet been studied.

Aim:

To investigate the correlation between HMWadiponectin

level and lipid profile in the type-2 diabetes mellitus (T2DM)-

Mets patients.

Method:

This is a cross sectional study with T2DM-Mets

patients who came to the outpatient clinic of Soetomo

Hospital in Surabaya during January 2010 to December 2012.

Subjects met the inclusion and exclusion criteria were mea-

sured their HMW adiponectin level in plasma using ELISA

method. Index lipid profilemeasuredwere serumhigh-density

lipoprotein cholesterol (HDL-C), triglyceride (TG), low-density

lipoprotein cholesterol (LDL-C), LDL/HDL ratio and TG/HDL

ratio. The study was approved by the local Research Ethics

Committee and subjects gave written informed consent.

Results:

Forty T2DM-Mets patients consisted of 16 (40%)

males and 24 (60%) females who met inclusion and exclusion

criteria were enrolled in this study. Their mean of age was

51 ± 5.2 years old, duration of illness was 16.49 ± 23.4 months,

HMW adiponectin level was 2,195.6 ± 4.6 ng/mL, A1C level

was 8.52 ± 0.9%, BMI was 26.62 ± 4.5 kg/m

, LDL-C level was

148.35 ± 31.1 mg/dL, triglyceride level was 173.00 ± 100.2 mg/

dL, HDL-C level was 48.15 ± 8.93 mg/dL, LDL/HDL ratio was

3.15 ± 0.7, and TG/HDL ratio was 3.78 ± 2.4. Spearman

’

s correl-

ation analysis showed that HMW adiponectin level was

significantly correlated with triglyceride level and TG/HDL

ratio (p = 0.009; r =

−

0.407 and p = 0.014; r =

−

0.387, respect-

ively). However, no significant correlation found with HDL-C,

LDL-C, and LDL/HDL ratio.

Conclusion:

Triglyceride cholesterol and TG/HDL ratio are

correlated with HMW adiponectin level in this T2DM-MetS

population.

PH-06

Fluoxetine treatment impairs E-cadherin-mediated cell

adhesion and altered calcium homeostasis in pancreatic beta

cells

Huang-Yu CHANG

, Shu-Ling CHEN

, Yun-Wen CHEN

Department of Pharmacology, College of Medicine, National Cheng

Kung University, Taiwan

Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65

–

S211

S180