We have screened a subtracted cDNA library in
order to identify differentially expressed genes in
omental adipose tissue of human patients with
Type 2 diabetes. One clone (&#x23;1738) showed a marked
reduction in omental adipose tissue from patients
with Type 2 diabetes. Sequencing and BLAST analysis
revealed clone &#x23;1738 was the adipocyte-specific
secreted protein gene apM1 (synonyms ACRP30,
AdipoQ, GBP28). Consistent with the murine orthologue,
apM1 mRNA was expressed in cultured
human adipocytes and not in preadipocytes.
Using RT-PCR we confirmed that apM1 mRNA
levels were significantly reduced in omental adipose
tissue of obese patients with Type 2 diabetes compared
with lean and obese normoglycemic subjects.
Although less pronounced, apM1 mRNA levels
were reduced in subcutaneous adipose tissue of
Type 2 diabetic patients. Whereas the biological
function of apM1 is presently unknown, the tissue
specific expression, structural similarities to TNF&#x3B1;
and the dysregulated expression observed in obese
Type 2 diabetic patients suggest that this factor
may play a role in the pathogenesis of insulin resistance
and Type 2 diabetes.

Michael A. Statnick

Lisa  S. Beavers

Laura J. Conner

Helena Corominola

Dwayne Johnson

Craig D. Hammond

Ronit Rafaeloff-Phail

Thomas Seng

Todd M. Suter

James P. Sluka

Eric Ravussin

Robert A. Gadski

Jose F. Caro

Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans
With Type 2 Diabetes

In the early 1980s, we proposed a unifying
model for β-cell damage (The OKAMOTO
model), in which poly(ADP-ribose) synthetase/
polymerase (PARP) activation plays an
essential role in the consumption of <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mrow><mml:mtext>NAD</mml:mtext></mml:mrow><mml:mtext>+</mml:mtext></mml:msup></mml:mrow></mml:math>,
which leads to energy depletion and necrotic
cell death. In 1984, we demonstrated that the
administration of PARP inhibitors to 90% depancreatized
rats induces islet regeneration.
From the regenerating islet-derived cDNA
library we isolated Reg (Regenerating Gene)
and demonstrated that Reg protein induces βcell
replication via the Reg receptor and ameliorates
experimental diabetes. More recently,
we showed that the combined addition of IL-6
and dexamethasone induces the Reg gene expression in β-cells and that PARP inhibitors
enhance the expression. In 1993, we found that
cyclic ADP-ribose (cADPR), a product synthesized
from <mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mrow><mml:mtext>NAD</mml:mtext></mml:mrow><mml:mtext>+</mml:mtext></mml:msup></mml:mrow></mml:math>, is a second messenger for
intracellular <mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mtext>Ca</mml:mtext><mml:mrow><mml:mtext>2+</mml:mtext></mml:mrow></mml:msup></mml:math> mobilization for insulin secretion
by glucose, and proposed a novel mechanism
of insulin secretion, the CD38-cADPR signal
system.Therefore, PARP inhibitors prevent β-cell
necrosis, induce β-cell replication and maintain
insulin secretion.In this paper, we would like to present a perspective
view based on our studies concerning
cell death, cell regeneration, and cell function,
especially on insulin-producing pancreatic βcells,
in the processes of which poly(ADPribose)
synthetase/polymerase (PARP) and
cyclic ADP-ribose (cADPR) are functioning.

Shin Takasawa

Hiroshi Okamoto

Pancreatic <svg style="vertical-align:-3.56264pt" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.162)"><path id="x1D6FD" d="M558 587q0 -32 -14 -61t-40 -53.5t-48.5 -41t-54.5 -36.5q144 -51 144 -174q0 -55 -43.5 -108t-104.5 -87q-77 -42 -131 -42q-31 0 -54 20t-31 47l11 18q48 -29 108 -29q79 0 119.5 43t40.5 109t-44.5 107.5t-119.5 50.5l22 47q34 1 65 21q96 61 96 157q0 42 -24 67.5&#xA;t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z" /></g></svg>-Cell Death, Regeneration and Insulin Secretion: Roles of Poly(ADP-Ribose) Polymerase and Cyclic ADP-Ribose

Anders A. F. Sima

Eleazar Shafrir

Editorial

Insulin resistance is the primary cause of type 2 diabetes.
However, if compensated by increased insulin production,
insulin resistance by itself does not lead to overt
disease. Type 2 diabetes develops when this compensation
is insufficient, due to defects in &#x3B2;-cell function and in regulation
of the &#x3B2;-cell mass. &#x3B2;-Cell transplantation, as well
as approaches that replenish or preserve the endogenous
&#x3B2;-cell mass, may facilitate the treatment of type 2 diabetes
in patients requiring exogenous insulin.

Shimon Efrat

&#x3B2;-Cell Expansion for Therapeutic Compensation of Insulin Resistance in Type 2 Diabetes

Background: The cytotoxic T lymphocyteassociated
antigen 4 gene (CTLA-4) encode the
T cell receptor involved in the control of T cell
proliferation and mediates T cell apoptosis.
The receptor protein is a specific T lymphocyte
surface antigen that is detected on cells only
after antigen presentation. Thus, CTLA-4 is
directly involved in both immune and autoimmune
responses and may be involved in the
pathogenesis of multiple T cell-mediated
autoimmune disorders. There is polymorphism
at position 49 in exon 1 of the CTLA-4 gene,
providing an A-G exchange. Moreover, we
assessed the CTLA-4 49 (Thr/Ala) polymorphism
in diabetic patients and first-degree relatives
as compared to control subjects.Research design and methods: Three loci
(HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 firstdegree
relatives and 84 nondiabetic control
subjects by means of PCR-RFLP.Results: A significant enrichment in DQB1
alleles encoding for an amino acid different
from Asp in position 57 (NA) and DQA1 alleles
encoding for Arg in position 52 was
observed in diabetic subjects and first-degree
relatives as compared to controls. The genotype
and allele frequencies of these polymorphisms
in type 1 diabetic patients and firstdegree
relatives differed significantly from
those of controls (p&#x3C; 0.001 and 0.05 respectively).
CTLA-49 Ala alleles frequencies were
75.8&#x25; in type 1 diabetic patients and 68.1&#x25; in
first-degree relatives in comparison to 35.7&#x25; in
control subjects. The Ala/Ala genotype conferred
a relative risk of 18.8 (p &#x3C; 0.001).Conclusion: The CTLA-4 49 Ala allele confers
an increased risk of type 1 diabetes, independent
of age and HLA-DQ genetic markers.

Jean Claude Ongagna

Remi Sapin

Michel Pinget

Alain Belcourt

Markers for Risk of Type 1 Diabetes in Relatives of Alsacian Patients With Type 1 Diabetes

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Journal of Diabetes Research publishes articles related to type 1 and type 2 diabetes. Topics include etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications such as nephropathy.

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Chief Editor Dr Mark Yorek, from the University of Iowa, is currently researching vascular and neural disease related to obesity and diabetes. His active research studies focus on etiology, treatment and prevention of nerve damage.

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title

Journal of Diabetes Research publishes articles related to type 1 and type 2 diabetes. Topics include etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications such as nephropathy.

Journal of Diabetes Research