Pancreatic Islets Aging in Old Rhesus Monkey

Abstract

BackgroundType 2 diabetes is an age associated disease which characterized by insulin resistance and loss of β cell mass and function. Accumulation of senescent β cells with age probably lead to compromised capacity of insulin synthesis and secretion. Nevertheless, other studies also suggested systemic aging may impair glucose tolerance via compromised peripheral insulin sensitivity and microcirculation. So, the pathophysiological process of pancreatic β cell senescence, and the relationship between senescent β cells and diabetes are not clarified. Rhesus monkey is one of the most ideal non‐human primate models of human aging. To date, the researches on islets function of rhesus monkeys, particularly aged monkeys are so limited. So, in this study, we are aiming to explore the link between islets senescence and diabetes in aged rhesus monkeys of approximately 20 years old that may reflect the characters of humans around 80 years old.MethodsSix middle age rhesus monkeys (average 10 years old) and six old rhesus monkeys (average 20 years old) were used in this study. Blood chemistry was detected and the intravenous glucose tolerance tests (IVGTT) were carried out. After sacrifice, the pancreatic islets were isolated to evaluate β cell function, and the histopathological analysis was done on the pancreatic tissues.ResultsIn the blood chemistry, no significant differences in kidney and liver functions were observed between the two groups. The old monkeys show slight increase on the fasting blood glucose, while their fasting insulin levels were increased distinctly. In addition, the IVGTT results showed that the glucose tolerance of the old group was slightly impaired, indicating the possible occurrence of peripheral insulin resistance. In respect to pancreatic histology, the immunohistochemistry staining with anti‐insulin antibody showed that both the total area of insulin producing β cells in pancreatic sections and the single islet mass decreased a lot in old rhesus monkeys, but interestingly, a notable elevated expression of pancreatic/duodenal homeobox‐1(PDX1), an important biomarker for β cell function, was observed. In respect to isolated islets, no significant difference was found in either glucose‐stimulated insulin secretion test(GSIS) or β‐Gal staining, suggesting the islets may function well in these old monkeys.ConclusionIn our 20 years old rhesus monkeys, the insulin resistance has appeared, and their islets area decreased obviously but not accompany significantly compromise of islets function, suggesting that the islets of old rhesus monkey may still have a strong compensatory ability.Support or Funding InformationThis study was supported by the Program of National Natural Science Foundation of China (81870609, 31571474, and 81571808), and the National Key Clinical Project.A, B, C) The fasting blood glucose, fasting blood insulin and intravenous glucose tolerance tests of middle age and old rhesus monkey. D) The glucose‐stimulated insulin secretion test (GSIS) of isolated isletsFigure 1E) The pancreatic sections immunohistochemistry staining with anti‐insulin antibody of middle age(left) and old(right) rhesus monkeyFigure 2