TY - JOUR
T1 - Age-related changes in pancreatic islet cell gene expression
AU - Giddings, Stephen J.
AU - Carnaghi, Lynn R.
AU - Mooradian, Arshag D.
N1 - Funding Information:
From the St. Louis Department of Veterans' Affairs Medical Center; Department of lnternal Medicine, Washington University; and Department of lnternal Medicine, St. Louis University, St. Louis, MO. Submitted January 13, 1994; accepted June 16, 1994. Supported in part by Medical Research Funds from the Department of Veterans Affairs (S.J. G. and A.D.M. ). Address reprint requests to Stephen J. Giddings, MD, PhD, Research Service (151 JC), John Cochran VA Medical Center, 915 N Grand Blvd, St. Louis, MO 63106. This is a US government work. There are no restrictions on its use. 0026-0495/95/4403-000750.00/0
PY - 1995/3
Y1 - 1995/3
N2 - Previous studies have indicated that insulin secretion in response to glucose diminishes with age but insulin synthesis and gene transcription do not. To determine whether expression of genes other than those that encode insulin are subject to age-related changes that could alter pancreatic islet function, mRNAs for insulins I and II, amylin, glucose transporter 2 (GluT2), glucagon, and glucokinase were quantified in 2-, 6-, 12-, and 24-month-old Fischer 344 rats using species-specific ribonuclease (RNase) protection assays. There was only a modest (1.2- to 1.3-fold) increase in insulin I and insulin II mRNAs between ages 2 and 12 months. There were no statistically significant changes in levels of glucokinase mRNA with age. In contrast, the abundances of amylin, GluT2, and glucagon mRNAs all doubled during the same period. Variance in values from 24-month-old rats was too great to allow conclusions, except that the ratio of insulin II mRNA to insulin I mRNA increased with age. This change was not related to islet mass or total insulin mRNA abundance because it persisted at age 24 months, when total mRNA abundance had decreased. These results indicate that aging is associated with significant alterations in the relative proportion of expression of pancreatic islet cell genes implicated in insulin secretion and in intraislet glucose metabolism.
AB - Previous studies have indicated that insulin secretion in response to glucose diminishes with age but insulin synthesis and gene transcription do not. To determine whether expression of genes other than those that encode insulin are subject to age-related changes that could alter pancreatic islet function, mRNAs for insulins I and II, amylin, glucose transporter 2 (GluT2), glucagon, and glucokinase were quantified in 2-, 6-, 12-, and 24-month-old Fischer 344 rats using species-specific ribonuclease (RNase) protection assays. There was only a modest (1.2- to 1.3-fold) increase in insulin I and insulin II mRNAs between ages 2 and 12 months. There were no statistically significant changes in levels of glucokinase mRNA with age. In contrast, the abundances of amylin, GluT2, and glucagon mRNAs all doubled during the same period. Variance in values from 24-month-old rats was too great to allow conclusions, except that the ratio of insulin II mRNA to insulin I mRNA increased with age. This change was not related to islet mass or total insulin mRNA abundance because it persisted at age 24 months, when total mRNA abundance had decreased. These results indicate that aging is associated with significant alterations in the relative proportion of expression of pancreatic islet cell genes implicated in insulin secretion and in intraislet glucose metabolism.
UR - http://www.scopus.com/inward/record.url?scp=0028929321&partnerID=8YFLogxK
U2 - 10.1016/0026-0495(95)90161-2
DO - 10.1016/0026-0495(95)90161-2
M3 - Article
C2 - 7885276
AN - SCOPUS:0028929321
SN - 0026-0495
VL - 44
SP - 320
EP - 324
JO - Metabolism
JF - Metabolism
IS - 3
ER -