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

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caveolin-1 mRNA into the NIT-1 cell and islet through the
latent virus infection then purified the positive infection cell
by puromycin containing(10 ug/mL) medium. First, we identi-
fied the change of gene expression profile in islet by mouse
gene expression microarray when the expression level of
caveolin-1 is down regulated and those pathways related with
beta cell proliferation and pancreatic secretion function were
found influenced much. Then we found the same result in the
NIT-1 cell strain. The differences of cell proliferate and
apoptosis among the caveolin-1 knockdown cell, the scramble
vector infection cell and the wildtype NIT-1 cell were
compared, and the effect of caveolin-1 on the cell’s prolifer-
ation and apoptosis were analyzed. The results of flow
cytometry and MTT show that knockdown the expression
level of caveolin-1 in NIT-1 cell could promote proliferation as
well as increase the resistance to palmitic acid ’s lipotoxicity.
The result of Real-time fluorescence quantification PCR show
that the expression level of casepase7 and caspase12 that
mediated the apoptosis process caused by endoplasmic
reticulum stress was downregulated according the down-
regulation of caveolin-1 expression in palmitic acid treated
NIT-1 cell strain. These findings suggest that caveolin-1 which
involved in the process of apoptosis and function regulation in
beta cell may serve as target for the development of novel
therapies for diabetes mellitus.
OL06-5
Disruption of peripheral clock gene Nocturnin leads to
defective islet beta cell function and glucose intolerance
Tien-Jyun CHANG 1, BIng-Mao CHEN1, Chih-Hao KUO1,
Meng-Wei LIU1, Siow-Wey HEE 1, Lee-Ming CHUANG1,2*.
1 Department of Internal Medicine, National Taiwan University
Hospital, 2Graduate Institute of Clinical Medicine, Medical College,
National Taiwan University, Taipei, Taiwan
Nocturnin is one of the circadian rhythmic “output gene”,
encodes a deadenylase – ribonuclease that specifically
removes the poly (A) tails from mRNAs. We investigated the
difference of glucose homeostasis, beta cell function, and
mRNA microarray between wild type (WT) and Nocturnin
knockout (NOC-/-) mice.
Bodyweight (BW), oral glucose tolerance test, insulin tolerance
test, isolated islet perifusion study, intrapancreatic insulin
content, immunohistochemical stain of insulin to measure
beta cell mass, micro-array of mRNA and microRNA were
performed and compared between wild type (WT) and NOC
(-/-) mice. Neither BW nor beta cell mass and insulin content
were different between WT and NOC (-/-) mice. NOC (-/-) mice
are more glucose intolerant but more insulin sensitive
than WT mice. Oral glucose-stimulated insulin secretion in
30 min is much less in NOC (-/-) mice than in WT mice. During
isolated islet perifusion study, the glucose stimulated
insulin secretion was much less in NOC (-/-) mice than in
WT mice. According to microarray study of mRNA of purified
islets, the gene expression levels of G protein coupled
receptor 18 (GPR 18), and hexokinase I (HK I) were much less
in NOC (-/-) mice than in WT mice. In islets from WT mice,
gene expression of GPR18 and HK1 showed prominent
circadian rhythm (night time >day time), which is compatible
with the circadian rhythm of Nocturnin gene expression.
However, the rhythmic change of these two genes was
dysregulated in NOC (-/-) mice. We also found the glucose-
stimulated insulin secretion (GSIS) was impaired in GPR18
knock-downMIN6 cells. Furthermore, we also found the GPR18
agonist, N-Arachidonylglycine (NAGLy) enhanced GSIS in islet
perifusion study of WT mic.
In conclusion, NOC plays a role in regulating glucose homeo-
stasis. Knock-out NOC gene leads to glucose intolerance with
impaired glucose-stimulated insulin secretion. The differ-
ences may attribute to the down-regulation and dysregulation
of GPR18 and HKI genes. It warranted to further investigate the
mechanism of GPR18 regulated by NOC and the role of GPR18
on glucose homeostasis.
OL06-6
Durability of diabetes remission after bariatric surgery: A 5-
year prospective follow-up in a multi-ethnic Asian population
Kwang Wei THAM1,3*, Phong Ching LEE1,3 , Hong Chang TAN1,3,
Alvin Kim Hock ENG2,3, Weng Hoong CHAN2,3,
Eugene Kee Wee LIM2,3, Sonali GANGULY1,3 . 1Department of
Endocrinology, Singapore General Hospital, 2Department of Upper GI
& Bariatric Surgery, Singapore General Hospital, 3Obesity &
Metabolic Unit, LIFE Centre, Singapore General Hospital, Singapore
With the advent of bariatric surgery, diabetes remission has
taken on a new perspective. One-year post-bariatric surgery
remission rates of type 2 diabetes mellitus (T2DM) have been
reported to be as high as 95%. Longer-term follow-up suggests
that relapse of DM in those who have remitted, is common.
However, such data is lacking, especially in Asia. We hereby
report the longer-term outcome of Asian T2DM patients, who
have undergone bariatric surgery.
Method: The prospective data of 100 patients with T2DM who
have undergone bariatric surgery at the Singapore General
Hospital with at least 2 years’ follow-up is analyzed. Complete
and partial DM remission are defined as HbA1c <6.0% and
<6.5% respectively without the use of DM medications. DM is
considered to have relapsed if the HbA1c rose to > 6.5% or if any
DM medication was used regardless of HbA1c.
Results: Of the 100 patients who underwent bariatric surgery
(sleeve gastrectomy 25%; gastric bypass 75%), 57% of them
were women and 47% were Chinese. Mean age was 50.0+/−9.2
years with a mean preop BMI of 39.1+/−7.6 kg/m2 . At 1 year
post-op, 80% achieved remission (71% complete, 9% partial). Of
those who have achieved DM remission at 1-year post-op, 12%
had DM relapse in the 2nd year, 25% in the 3rd year, 30% in the
4th year and 37% by the 5th year. At the end of 5 years, only 36%
remained in complete remission while 7% were in partial
remission with 57% either never achieving remission or had
DM relapse. Compared with those who achieved DM remission
at 1-year post-op but relapsed into the DM range subsequently,
those who achieved sustained DM remission for at least 2
years, had lost significantly more weight (mean weight loss
27.3+/−9.6% vs 9.3%+/−0.8%; p = 0.001), and pre-operatively,
had significantly shorter mean duration of DM (55+/− 59
months vs 157+/− 120 months; p = 0.032) and lower HbA1c
(7.9+/−1.3% vs 8.6+/−1.1%; p = 0.012), without any significant
differences in pre-op BMI.
Conclusion: Bariatric surgery in T2DM patients is associated
with sustainable DM remission in a substantial proportion.
However, prospective long-term follow-up is crucial as up to
50% of those who achieve DM remission at 1-year post-op may
develop DM relapse at 5 years post-op. Patients with longer DM
duration, poorer glycemic control preop and those who attain
less weight loss post-op seem to be at higher risk for relapse.
OL06-7
Metabolic surgery for Type 2 Diabetes Mellitus in young-onset
patients
Tan Chun HAI1,2, Wei-Jei LEE2, Nawaf ALKHALIFAH2,3,
Shu-Chu CHEN2, Jung-Chien CHEN2 , Kong-Han SER MD2.
1Department of Surgery, Khoo Teck Puat Hospital, Singapore;
2Department of Surgery, Min-Sheng General Hospital, Taiwan;
3Department of Surgery, AlAdan Hospital, Kuwait
Background: The prevalence of young onset Type 2 Diabetes
Mellitus (T2DM) is increasing and it is known to respond poorly
to medical treatment. Metabolic Surgery has been well
recognized for its effectiveness in remission of T2DM but its
effectiveness and durability on remission of diabetes in young
onset T2DM has not been explored so far.
Oral Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S40–S64 S54