Main content area

Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

Wang, Fei, Kohan, Alison B., Kindel, Tammy L., Corbin, Kathryn L., Nunemaker, Craig S., Obici, Silvana, Woods, Stephen C., Davidson, W. Sean, Tso, Patrick
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.24 pp. 9641-9646
absorption, animal disease models, blood glucose, calcium, cyclic AMP, diabetes mellitus, fasting, glucose, glucose tolerance, high fat diet, homeostasis, hyperglycemia, insulin, insulin secretion, islets of Langerhans, lipids, mice, small intestine
Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca ²⁺ influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV ⁻/⁻ mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV ⁻/⁻ mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.