Grant-in-Aid for Scientific Research (B).
|Research Institution||Wakayama University of Medical Science|
SANKE Tokio Wakayama Univ. of Med. Sci. Dept. of Med. Associ. Prof., 医学部・第一内科, 講師 (20187305)
NISHIMURA Susumu Wakayama Univ. of Med. Sci. Dept. of Med, Assoc. Prof., 医学部・第一内科, 講師 (10172694)
KONDO Michi Wakayama Univ. of Med. Sci. Dept. of Med, Assoc. Prof., 医学部・第一内科, 助教授 (60137289)
NANJO Kishio Wakayama Univ. of Med. Sci. Dept. of Med, Prof., 医学部・第一内科, 教授 (40164511)
|Project Fiscal Year
1989 – 1990
Completed(Fiscal Year 1990)
|Budget Amount *help
¥6,800,000 (Direct Cost : ¥6,800,000)
Fiscal Year 1990 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1989 : ¥5,700,000 (Direct Cost : ¥5,700,000)
|Keywords||Islet Amyloid Polypeptide / Amylin / Diabetes Mellitus / Amyloid / 膵ラ氏島アミロイド蛋白 / アミリン / 糖尿病 / アミロイド / IAPP / 血中濃度 / IAPP遺伝子 / ホルモン分泌 / RFLP / インスリン感受性|
1. Secretion of IAPP
IAPP was co-secreted with insulin from neonatal rat cultured islet cells by glucose or non-glucose (arginice, tolbutamide and glucagon) stimuli. Basal secretion ratio of IAPP to insulin was 1 : 17 in molar basis.
2. Actions of synthesized IAPP-amide
(A) Effects of IAPP on hormones secretion in pancreatic islet
IAPP (1X10^<-9>-1X10^<-7>M) had no effects on insulin secretion by glucose or glucagon secretion by arginine or low glucose from meonatal rat islet culture cells.
(B) Effects of IAPP on insulin sensitivity in vivo in dogs
In hyperinsulinemic euglycemic glucose clamp test in dogs, IAPP infusion (107pg/kg/min) caused peripheral insulin resistance.
(C) Effects of IAPP on hepatic glucose output
In rat liver perfusion, IAPP (1X10^<-12>-1X10^<-7>M) had no effects on hepatic glucose output induced by glucagon and on inhibitory action of insulin to hepatic glucose output. IAPP alone had also no effect on hepatic glucose output. Extraction of physiological dose of IAPP from t
he liver was negligible in contrast to 50% of hepatic insulin extraction.
(D) Effects of IAPP on insulin action in isolated rat fat cells
IAPP (1x10^<-8>M) had no effects on insulin induced glucose oxidation in isolated rat fat cells.
3. Peripheral plasma level of IAPP in human
Fasting plasma IAPP concentration in normal control subjects was about 6.4x10^<-12>M. The peripheral molar ratio of IAPP to insulin was about 1 : 7. Molar ratio of fasting plasma IAPP to C-peptide in patients with non-insulin dependent diabetes mellitus (NIDDM) was significantly lower than that in control subject, suggesting that basal hypo-secretion of IAPP relative to insulin exists in NIDDM.
Plasma IAPP increased by oral glucose load and decreased by insulin hypoglycemia or hyperinsulinemia. These behavior of plasma IAPP were similar to that of insulin or C-peptide.
Obese patients who had hyperinsulinemia relative to C-peptide had hyper-response of IAPP relative to C-peptide compared to non-obese patients, suggesting that IAPP has some physiological action to modulate glucose metabolism.
4. RFLP of the human IAPP gene
Two IAPP allele polymorphism were found by RFLP analysis using genomic DNA. However, no significant difference in frequency of the each allele could be found between NIDDM patients and control subjects Less