Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets. Issue 2 (4th March 2019)

• Record Type: Journal Article
• Authors: Cho, Jung Hoon; Lee, Kyeong-Min; Lee, Yun-Il; Nam, Hong Gil; Jeon, Won Bae
• Is Part Of: Islets. Volume 11:Issue 2(2019)
• Page Start: 33
• Page End: 43
• Publication Date: 2019-03-04
• Subjects: Aging -- GAD67 -- pancreatic islets -- insulin secretion; Islands of Langerhans -- Periodicals; Pancreas -- Periodicals; 616.46
• DOI: 10.1080/19382014.2019.1599708
• Languages: English
• ISSNs: 1938-2022

Abstract

ABSTRACT: Pancreatic islets play an essential role in regulating blood glucose levels. Age-dependent development of glucose intolerance and insulin resistance results in hyperglycemia, which in turn stimulates insulin synthesis and secretion from aged islets, to fulfill the increased demand for insulin. However, the mechanism underlying enhanced insulin secretion remains unknown. Glutamic acid decarboxylase 67 (GAD67) catalyzes the conversion of glutamate into γ-aminobutyric acid (GABA) and CO2 . Both glutamate and GABA can affect islet function. Here, we investigated the role of GAD67 in insulin secretion in young (3 month old) and aged (24 month old) C57BL/6J male mice. Unlike young mice, aged mice displayed glucose-intolerance and insulin-resistance. However, aged mice secreted more insulin and showed lower fed blood glucose levels than young mice. GAD67 levels in primary islets increased with aging and in response to high glucose levels. Inhibition of GAD67 activity using a potent inhibitor of GAD, 3-mercaptopropionic acid, abrogated glucose-stimulated insulin secretion from a pancreatic β-cell line and from young and aged islets. Collectively, our results suggest that blood glucose levels regulate GAD67 expression, which contributes to β-cell responses to impaired glucose homeostasis caused by advanced aging.