Age-dependent reduction in insulin secretion and insulin mRNA in isolated islets from rats.
Aging is an etiologic factor in non-insulin-dependent diabetes mellitus. To characterize the beta-cell abnormalities that occur with age, we investigated glucose-stimulated insulin release, pancreatic insulin content, and mRNA levels for islet-specific genes in aging Wistar rats. Ten minutes after glucose stimulation, 6-mo-old islets had approximately 40% more cells secreting insulin than 24-mo-old islets (P < 0.0001); after 1 h, 67 +/- 1.0% islets from 6-mo-old rats secreted insulin, compared with 51 +/- 3.5% from 24-mo-old rats (P < 0.0001). The amount of insulin secreted by each beta-cell was also less in the older animals (P < 0.0001). Despite increases in islet size (P < 0.0001) and beta-cell number (P < 0.0001) with age, whole pancreas insulin content showed that 24-mo-old pancreas had less insulin than 6-mo-old pancreas (0.61 +/- 0.06 vs. 0.84 +/- 0.08 microgram/mg pancreatic protein; P < 0.05). Finally, insulin mRNA levels declined to 50% of the newborn value in 24-mo-old islets (P < 0.0001), whereas glucagon mRNA levels showed a very modest decline with age. Somatostatin mRNA levels did not vary significantly. In summary, it appears that in Wistar rats there is a progressive decline in beta-cell activity with age. This decline may represent the biological features of the age-dependent risk of developing diabetes.
Perfetti
R
R
Diabetes Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Rafizadeh
C M
CM
Liotta
A S
AS
Egan
J M
JM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D005934:Glucagon / Q000235:genetics; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D015335:Molecular Probes; D012333:RNA, Messenger; D013004:Somatostatin; D005934:Glucagon