Abstract
BackgroundExperiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes.MethodsA naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls).ResultsWe found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes.ConclusionDisruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-016-0088-8) contains supplementary material, which is available to authorized users.
Highlights
Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis
All participants were of self-reported European ancestry. 69,854 individuals without type 2 diabetes were available for the analysis of fasting glucose levels
We found no evidence for association of p.Q121X with fasting glucose levels (beta = 0.002 mmol/L; 95 % conference interval[CI] = (-0.025, 0.029); p-value = 0.90) (Table 1)
Summary
Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. In type 1 and to a lesser extent in type 2 diabetes, the insulin-producing beta cells of the pancreas undergo destruction and exhibit decreased function. A study in mice demonstrated that pancreatic beta cell proliferation is stimulated by a 198-amino acid protein named betatrophin Findings in model systems suggest that whereas a role for ANGPTL8 in beta cell proliferation is uncertain, ANGPTL8 is consistently linked to triglyceride concentrations. We have previously reported a naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call