Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Speech Abstracts

Keynote Lecture

KN-01

Adiponectin and its receptors: A major role in type 2 diabetes

and obesity-linked diseases

Takashi KADOWAKI

Department of Diabetes and Metabolic

Diseases, Graduate School of Medicine, The University of Tokyo

Adiponectin is an adipocyte hormone that is most abundantly

expressed in white adipose tissue, whose function was

entirely unknown. We and others discovered that adiponectin

enhances insulin sensitivity and possesses anti-diabetic

actions. We subsequently identified and cloned the receptors

of adiponectin (AdipoR1 and AdipoR2), which represent a

new receptor superfamily containing seven-transmembrane

domains. AdipoR1 and AdipoR2 regulate the burning of

glucose and fatty acids and enhance insulin sensitivity.

In obese subjects, the expression of not only adiponectin but

also AdipoR1 and AdipoR2 is reduced, which is the main cause

of various diseases associated with obesity such as type 2

diabetes, metabolic syndrome, cardiovascular disease and

short life. We developed a small-molecule adiponectin recep-

tor agonist (AdipoR Agonist: AdipoRon) and showed that orally

administered AdipoRon activates the same signaling pathway

as caloric restriction and physical exercise, thereby improving

obesity-related diseases as a whole, including type 2 diabetes,

and actually working as a health- and longevity-promoting

drug. Most recently, we succeeded in elucidating the three-

dimensional structure of adiponectin receptors, and is con-

ducting research toward identifying the mechanism of adipo-

nectin actions at the atomic level, and optimizing adiponectin

receptor agonists, based on the three-dimensional structure

data.

Plenary Lecture

PL-01

Diabetes: Is this the greatest epidemic in the history of

mankind

Paul ZIMMET

Monash University, Melbourne, Australia

Diabetes has been seriously underrated as a global public

health issue. The last three decades have witnessed an epide-

mic rise in the number of personswithdiabetes, especially type

2 diabetes. The main burden lies in developing nations where

more than 80% of the people with diabetes live. While aging,

urbanization and associated lifestyle changes are the major

determinants for the rapid increase, adverse intrauterine

environmental and the resulting epigenetic changes may be

major factors contributing to the epidemic inmany developing

countries. Diabetes risk through epigenetic changes can be

transmitted inter-generationally thus creating a vicious cycle

that will continue to feed the diabetes epidemic. History

provides important lessons such as those from major cata-

strophic events such as the Dutch Winter Hunger and Chinese

famines. The Chinese famine may have been the trigger for

what may be viewed as a diabetes

“

avalanche

”

many decades

later in China. More than 60%of the peoplewith diabetes live in

Asia with almost one third in China. The spectacular rise in

diabetes poses huge social and economic problems to most

nations in Asia and could impede national and regional

development. More action is required to understand the

drivers of the epidemic to provide the rationale for prevention

strategies. Unless drastic steps are taken through national

prevention programmes to curb the escalating trends in all the

countries, the social, economic and health care challenges are

likely to be insurmountable. More reliable estimates of the

future burden of diabetes are urgently needed. It is apparent

that the IDF have consistently underestimated the global

burden. In 2011, their estimate was already 371 million people

with diabetes yet this had earlier been predicted as the forecast

20 years hence for 2030. Type 2 diabetes will remain one of the

greatest challengestohumanhealthformanyyearstocome. To

meet the challenge we must also direct attention to see which

countries may bear the brunt of diabetes in the future and to

plan the resources need to address it.

PL-02

From p-values to proteins: Using genetic and genomic data to

deliver biological insights and clinical opportunities for type 2

diabetes

Marc M

CARTHY

1,2

Wellcome Trust Centre for Human Genetics,

University of Oxford,

Oxford Centre for Diabetes, Endocrinology and

Metabolism, University of Oxford, Oxford, UK

The growing prevalence of type 2 diabetes highlights the limi-

tations of available preventative options, and high rates of

diabetes complications attest to the inadequacies of current

treatments. Novel therapeutic strategies need to be infor-

med by a more complete understanding of the molecular

and physiological basis of disease, delivering validated inter-

ventional targets and biomarkers to define disease risk,

progression, and subtype.

My group, working within large global consortia, uses human

genetics to deliver this understanding. Growing availability

of exome sequence and array data now delivers coding variant

associations that can plug directly into functional studies.

However, the main repository of variant association for

T2D remains

∼

100 common variant signals uncovered by

GWAS, most of which map outside coding sequence. We are

implementing a multifaceted approach that combines

genome-scale and focused functional studies to unlock the

biology within these loci.

We use fine-mapping to improve localisation of causal

variants, and map these onto regulatory annotations from

key tissues, most notably the human islet. This provides

a platform for identifying downstream transcripts through

D IABETES R ESEARCH AND C LINICAL P RACTICE 120S1 (2016) S1 – S39

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