Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

compare radiolabeled probe accumulation with other, con-

ventional methods for quantification of BCM. In this sympo-

sium, I present our up-to-date data on this non-invasive

method of evaluation of beta-cell mass.

S26-2

Magnetic resonance imaging of islet grafts

Jyuhn-Huarng JUANG

Division of Endocrinology and

Metabolism, Department of Internal Medicine, Chang Gung

University and Chang Gung Memorial Hospital, Taoyuan, Taiwan

The development of islet imaging techniques can improve the

diagnosis and characterization of diabetes mellitus. Recently,

noninvasive magnetic resonance imaging (MRI) has been used

to monitor the mass, function, death, vascularity, innervation,

autoimmune activation and infiltration of endogenous and

grafted islets in animals and humans.

Although islet transplantation is a promising approach,

substantial graft loss can occur owing to allorejection, auto-

immune attack, glucotoxicity, mechanical stress and micro-

environmental disruption of the islets during transplantation.

The use of MRI to assess transplanted islets can help to

optimize transplantation protocols, explore the anatomy and

physiology of transplanted islets and study the immunology

of islet engraftment. In the past years, MRI has been used to

detect transplanted islets labeled with dextran-coated super-

paramagnetic iron oxide (SPIO), such as ferumoxide (Feridex

Endorem

™

) and ferucarbotran (Resovist

) in mice, rats,

baboons, nonhuman primates, and humans. In 2010, Saudek

et al. first reportedMR detection of ferucarbotran-labeled islets

up to 24 weeks in the liver of 8 C-peptide negative diabetic

recipients.

Recently, we developed an in situ coating method for pre-

paring ferrofluids coated with

-ray irradiated chitosan and

proved that the chitosan-coated SPIO (CSPIO) nanoparticles

have potential as an MR T2 contrast agent. In addition, we

demonstrated that CSPIOnanoparticles were taken up by islets

in vitro, did not affect insulin secretion and death rates of

islets, and could be visualized by MR imaging for long-term

tracking of mouse islet isografts and allografts.

In conclusion, MRI represents a valuable platform for a

thorough investigation of transplanted islets. In the future,

repeated systemic administration of

-cell specific agents to

islet recipients and multimodality approaches, such as PET

–

MRI, would enable the method to be used in a wide variety of

diagnostic and therapeutic applications in diabetes.

Orally Administered Antidiabetic Agents

S11-3

Multifunctional nanoparticles for oral protein drug delivery

Er-Yuan CHUANG

, Kun-Ju LIN

2,3

, Fang-Yi SU

, Fwu-Long MI

Chiung-Tong CHEN

, Jyuhn-Huarng JUANG

Hsing-Wen SUNG

Department of Chemical Engineering/Institute

of Biomedical Engineering, National Tsing Hua University, Hsinchu,

Healthy Aging Research Center, Department of Medical Imaging and

Radiological Sciences, College of Medicine, Chang Gung University,

Department of Nuclear Medicine and Molecular Imaging Center,

Chang Gung Memorial Hospital, Taoyuan,

Department of

Biochemistry, School of Medicine, College of Medicine, Taipei Medical

University, Taipei,

Instituteof Biotechnology and Pharmaceutical

Research, National Health Research Institutes, Zhunan, Miaoli,

Division of Endocrinology and Metabolism, Chang Gung University

and Chang Gung Memorial Hospital, Taoyuan, Taiwan

Calcium (Ca

) has a crucial role in maintaining the intestinal

protease activity and in forming the apical junctional complex

(AJC) that preserves epithelial barrier function. Ethylene glycol

tetraacetic acid (EGTA) is a Ca

-specific chelating agent. To

maintain the concentration of this chelator in areas where

enzyme inhibition and paracellular permeation enhancement

are needed, this study synthesized a poly(

-glutamic acid)-

EGTA conjugate (

PGA-EGTA) to form nanoparticles (NPs) with

chitosan (CS) for oral insulin delivery. Results of our mole-

cular dynamic (MD) simulations indicate that Ca

ions could

be specifically chelated to the nitrogen atoms, ether oxygen

atoms, and carboxylate oxygen atoms in [Ca(EGTA)]

–

anions.

By chelating Ca

PGA-EGTA conferred a significant insulin

protection effect against proteases in intestinal tracts isolated

from rats. Additionally, calciumdepletion by

PGA-EGTA could

stimulate the endocytosis of AJC components in Caco-2 cell

monolayers, which led to a reversible opening of AJCs and

thus increased their paracellular permeability. Single-photon

emission computed tomography images performed in the

biodistribution study clearly show the

123

I-insulin orally

delivered by CS/

PGA-EGTA NPs in the heart, aorta, renal

cortex, renal pelvis and liver, which ultimately produced a

significant and prolonged hypoglycemic effect in diabetic rats.

The above results confirm that this

PGA-EGTA conjugate is

a promising candidate for oral insulin delivery.

Injectable Antidiabetic Agents (I): GLP-1

Receptor Agonists

S18-1

Pleiotropic actions of GLP-1 RA

Young Min CHO

Department of Internal Medicine, Seoul National

University College of Medicine, Seoul, Korea

Glucagon-like peptide 1 (GLP-1) is an incretin hormone secre-

ted primarily from the intestinal L-cells in response to meals

which modulates nutrient homeostasis via actions exerted in

mutliple tissues and cell types. GLP-1 and its analogs, as well

as compounds that inhibit endogenous GLP-1 breakdown,

have become an effective therapeutic strategy for many

subjects with type 2 diabetes. Considering the wide distribu-

tion of the GLP-1 receptor, it is perhaps unsurprising the GLP-1

exerts pleiotropic effects beyond glucose lowering. These

include appetite regulation, inhibition of gastric acid secretion

and gastric emptying, regulation of hepatic glucose produc-

tion, regulation of cardiac function and bone resorption, and

cardiovascular effects. In this lecture, I will review pancreatic

and extrapancreatic effects of GLP-1.

S18-2

Incretin-based therapy on diabetic nephropathy

Yuichiro YAMADA

, H. FUJITA

, S. TAKASHIMA

, T. NARITA

Department of Endocrinology, Diabetes and Geriatric Medicine,

Akita University Graduate School of Medicine, Akita, Japan

Incretin-based anti-hyperglycemic drugs, DPP-4 inhibitors and

GLP-1 receptor agonists, arewidely used for treatment of type 2

diabetes. Incretin was originally designated as a gut-derived

insulinotropic factor. Because receptors of incretin are expres-

sed not only in pancreatic

-cells but also in extra-pancreatic

tissues(1), extra-pancreatic effects in addition to pancreatic

effects are expected. Furthermore, DPP-4 can inactivate several

peptide hormones in addition to incretin,

“

incretin

”

and

“

beyond incretin

”

effects are also expected.

We have shown that GLP-1 receptors are expressed in glo-

merular capillary and vascular walls, but not in tubuli, in the

mouse kidney. C57BL/6-Akita mice are diabetic and nephro-

pathy-resistant. We have generated C57BL/6 Akita GLP-1

receptor-deficient mice and revealed that these mice have

higher urinary albumin levels and more advanced meangial

expansion than C57BL/6-Akita mice, despite comparable

levels of hyperglycemia. KKTa-Akita mice are diabetic and

nephropathy-prone and treatment of these mice with

Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1

–

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