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KMID : 0882419930450010025
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Korean Journal of Medicine
1993 Volume.45 No. 1 p.25 ~ p.37
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The Clinical Characteristics of Korean adult-onset Diabetics with ICSA and the Effect of ICSA on Insulin Secretion in Isolated Rat Islets
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우정택
김덕윤/김성운/양인명/김진우/김영설/김광원/최영길
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Abstract
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bjectives : It is well known that typeⅠand tipe Ⅱ diabetes have clincally distinct features each other. The pathogenesis of type Ⅰis related to autoimmune destruction of beta cell characterized by the presence of autoantibodies such as ICA and
ICSA.
Also, it is well known that more than 80% of NIDDM are obese in Caucasian. However,
in Korea more than 70% of NIDDM are not obese and many of them are insulin-required. It
can be postulated that some portion of Korean type Ⅱ diabetes are different from caucasion
type Ⅱ diabetes in its pathogenesis.
Therefore, we studied the prevalence of ICSA positivity in Korean patients with NIDDM
and the functional role of ICSA on insulin secretion.
Methods : 2001 patients with adult-onset diabetes and 200 non-diabetic normal control
were included. The ICSA assay was done by 51Cr releasing assay with the RINm5F cell line.
The effect of ammonium precipitated immunoglobulin from ICSA-positive patients on insulin
secretion and phosphoinositide hydrolysis were studied with perifusion of isolated rat islets.
Nothern blot analysis was done to study the effect of imunoglobulin from ICSA positive
patients on glucokinase or GLUT 2 mRNA expression in HIT-T15 cells. cAMP was
measured to study the effect of immunoglobulin from ICSA positive patients on cAMP
production of HIT-T15 cell.
Results :
1) The prevalence rate of the ICSA in Korean patients with NIDDM was 7.05% which
was significantly higher than that (2%) in normal subject (p<0.05).
2) The Korean patients with ICSA positive NIDDM were characterized by marked weight
loss, poor glycemic control and significantly reduced insulin secretory response.
3) Inhibitory effect of serum immunoglobulins from the diabetics with ICS A on insulin
secretion of beta-cells induced by glucose stimulation was confirmed by the perifusion
system.
4) The suggested mechanisms of ICSA on insulin secretion are inhibition of glucokinase
and glucose transporter 2mRNA expression inhibition of phosphoinositide hydrolysis metabolic
pathway
Conclusion : There is a certain group of adult onset diabetes still unclassified but
haracterized by appearance of ICSA, marked weight loss and markedly reduced insulin
secretion and finally becoming insulin dependent.
The ICSA detected in this group of adult onset diabetics may also play a role in an effect
on multiple steps of signal transduction pathways related to insulin secretory mechanism.
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KEYWORD
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