Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

WT-HFD, however, those peaks shifted to 13:00 and 1:00,

respectively. In WT-CD, a marked increase of COUNT was

observed both at the beginning and at the end of dark phase

concomitant with an increase of FI in these periods. These

increases were weakened inWT-HFD andmarkedly reduced in

GKO-CD. To verify a role of ghrelin as an initiator of voluntary

exercise, we further tested effects of ghrelin agonist (GHRP6)

injection (ip) on COUNT in GKO-CD at 16 weeks old. A single

injection of GHRP6 (1 mg/kg) at 18:30 for 2 weeks brought about

a significant enhancement of COUNT during dark phase

in spite of no effect of continuous administration of this

agent by osmotic pumps at the same dose.

It was thus clearly demonstrated that ghrelin surges at 7:00 and

19:00 observed inWT-CDplay a crucial role in the initiation and

motivation of voluntary exercise in these periods. Because

diurnal ghrelin rhythm were disturbed in WT-HFD concomi-

tant with the decrease of COUNT, therapeutic properties of this

peptide are to be further elucidated in future investigations.

OL02-4

Attenuation of high fatty acid-induced hepatic lipotoxicity and

insulin resistance by induction of miR-302

Hsin-Hua LI

, Chih-Li LIN

, Chiung-Huei PENG

Chien-Ning HUANG

1,3,4

Institute of Medicine, Chung-Shan

Medical University,

Division of Basic Medical Science, Hungkuang

University,

Department of Internal Medicine, Chung-Shan Medical

University Hospital,

School of Medicine, Chung-Shan Medical

University, Taiwan

Non-alcoholic fatty liver disease (NAFLD) is a very common

disorder and characterized by the accumulation of excess fat

in the liver. Hepatic insulin resistance is a typical feature of

NAFLD, which represents the precursor stage of type 2 dia-

betes. Increased lipid accumulation leads to interfere with

hepatic metabolism, which in turn stimulates oxidative

stress and lipotoxicity and subsequently induces hepatic

damages including inflammation, senescence and apoptosis.

As a result, inhibition of hepatic fatty acid formation and

accumulation represents a valid therapeutic strategy for the

treatment of NAFLD. Recently, many studies have demon-

strated that several microRNAs (miRNAs) contribute to the

pathogenesis of NAFLD. Particularly, miR302 is predicted as a

repressor in fatty acid synthesis by targeting at elongation of

very long chain fatty acids-6 (Elovl6), a key enzyme produces

long chain fatty acids in the liver. Elovl6 regulates the

composition of fatty acid in cells and affects some inflamma-

tory factor activity, which influences the occurrence and

development of NAFLD and hepatic insulin resistance. In

addition, we have previously demonstrated that upregulation

of miR302 is able to alleviate neuronal insulin resistance by

slowing aging process, suggesting miR302 may exert potential

benefits in preventing NAFLD. As both hepatic insulin

resistance and cellular senescence are two major factors in

the pathogenesis of NAFLD, we speculate that miR302 may

display protective roles in NAFLD. However, the detailed

molecular mechanisms underlying miR302 in NAFLD patho-

genesis are still largely unclear. In the present study, we

demonstrated that palmitic acid and oleic acid mixture can

induce the formation of fatty acid, total lipid and triglyceride

(TG), which close resemble to NAFLD. However, overexpres-

sion of miR-302 may attenuate fatty acid-induced lipid

accumulation. Moreover, overexpressed miR-302 not only

attenuates lipotoxicity, but also prevents insulin resistance,

oxidative stress, senescence and mitochondria dysfunction by

targeting to Elovl6 in HepG2 cell. In conclusion, our results

provided some details of miR302 at molecular basis involved in

the pathogenesis of NAFLD. Accordingly, restoration of hepatic

insulin signaling by upregulation of miR302 may display

potential implications to develop novel preventive, diagnostic,

or therapeutic strategies in NAFLD.

OL02-5

One-year post-transplant hyperglycemia aggravated kidney

function in diabetic patients

Takako YONEMOTO

*, Hiroshi HATAKEYAMA

Kouhei SAITOH

, Chika KYO

, Rieko UMAYAHARA

Tatsuo OGAWA

, Tatsuhide INOUE

Shizuoka General Hospital,

Japan

Background:

The efficacy of kidney transplantation in diabetic

patients is well known; however, immunosuppressive treat-

ment with steroids after surgery contributes to insulin

resistance, bulimia, obesity, and hyperglycemia. Furthermore,

functional kidney recovery contributes to an increase in the

required amount of insulin, and more antidiabetic medica-

tions are needed after transplantation in some cases.

Objective:

This retrospective study included 12 chronic renal

failure patients who underwent kidney transplantation

between 2008 and 2014 in Shizuoka General Hospital.

Changes in HbA1c, GA, urine albumin, and eGFR levels were

assessed at 6 months, 1, and 2 years after transplantation.

Results:

One patient was diagnosed with acute rejection,

requiring dialysis soon after transplantation. Therefore, we

assessed the 11 remaining patients: 8 men and 3 women, one

with type 1 and 11 with type 2 diabetes, and average age of

48.5 ± 11.7 years.

Before surgery, 4 patients used injectable insulin (average,

20.5 U/day), 2 patients took oral antidiabetic medication (DPP4

inhibitors), and 5 did not take diabetic medication.

One year later, all patients were being treated with diabetic

drugs: 8 with injectable insulin (mean, 32.3 U/day) and 3 with

oral antidiabetic medication.

Although, the treatment of diabetes was more intensive than

before surgery, blood glucose controls worsened after surgery

(HbA1c: pre, 6.6 ± 1.1%; 1 year later, 8.0 ± 1.8%; GA: 19.1 ± 3.9%,

25.7 ± 9.7%).

The eGFR levels were improved by transplantation (5.3 ± 2.1

mL/min/1.73 m

, 43.6 ± 7.3 mL/min/1.73 m

). Urine albumin

was detected 1 year later (average, 91.0 ± 119.0 mg/g

•

Cr),

including 5 patients (45%) above 30 mg/g

•

Cr.

There was a correlation between urine albumin at 1 year and

glycemic control markers (GA at pre-transplantation: r = 0.80,

p = 0.03; HbA1c at 1 year: r = 0.86, p = 0.006).

There was no correlation between eGFR at 1 year and glycemic

control markers.

Mental disease (e.g., developmental disorders, hysteria, and

depression) is a risk factor of aggravation of renal function.

Discussion and conclusion:

Post-transplant hyperglycemia

affected kidney function at 1 year in diabetic patients in this

study.

As previously reported, the pathological recurrence of diabetic

kidney disease can appear as early as 2 years after kidney

transplantation.

Patients with psychiatric problems occasionally are noncom-

pliant for glycemic control, pre- and post-transplantation,

which contributes to rapid progression of kidney failure.

We need to carefully consider diabetes self-management

ability and education before kidney transplantation.

OL02-6

Abrogation of Toll-like receptor 4 (TLR4) mitigates obesity-

induced insulin resistance and glucose intolerance through

reducing mitochondrial ROS in visceral fat

Hung-Yu LIN

, Pei-Wen WANG

*, Shao-Wen WENG

Hsiao-Mei KUO

, Chia-Shiang CHANG

, Ching-Yi LIN

Cheng-Feng TSAO

Department of Internal Medicine, Kaohsiung

Chang Gung Memorial Hospital and Chang Gung University College

of Medicine, Kaohsiung, Taiwan

Obesity-induced excessive visceral fat (VF) accumulation is

associated with insulin resistance and systemic oxidative

stress and chronic inflammation. Toll

–

like receptor 4 (TLR4)

plays an important role in innate immunity and chronic

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