Hypersecretion of IAPP from the islets of VMH-lesioned rats and obese Zucker rats.
To investigate the possible role of islet amyloid polypeptide (IAPP) in the development of type 2 diabetes mellitus, we examined the IAPP content and secretion in pancreatic islets isolated from ventromedial hypothalamic (VMH)-lesioned rats and genetically obese Zucker rats, using a specific radioimmunoassay for IAPP. Obesity and hyperinsulinemia were observed in rats 21 days after VMH lesioning. IAPP content was increased in the islets of VMH-lesioned rats compared with findings in the sham-operated controls (100.9 +/- 6.6 vs 72.8 +/- 3.85 fmol/islet; P less than 0.01). Isolated islets of VMH-lesioned rats secreted larger amounts of IAPP in the presence of 2.8 and 16.7 mM glucose (2.99 +/- 0.98 and 11.2 +/- 0.29 fmol islet-1 3 h-1) than was noted in sham-operated rats (ND and 6.65 +/- 0.78 fmol islet-1 3 h-1). In the obese Zucker rats, aged 14 weeks, IAPP concentrations in the islets were elevated compared with lean rats (133.3 +/- 10.6 vs 84.4 +/- 8.5 fmol/islet; P less than 0.01). The isolated islets secreted larger amounts of IAPP in response to 2.8 and 16.7 mM glucose (2.83 +/- 0.88 and 15.81 +/- 1.35 fmol islet-1 3 h-1) than did those from lean control rats (0.36 +/- 0.19 and 12.49 +/- 1.20 fmol islet-1 3 h-1). These results strongly suggest that overproduction and hypersecretion of IAPP occur in animals with obesity and hyperinsulinemia.
Tokuyama
Y
Y
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Kanatsuka
A
A
Ohsawa
H
H
Yamaguchi
T
T
Makino
H
H
Yoshida
S
S
Nagase
H
H
Inoue
S
S
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D012016:Reference Values; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide