Abstract
Pancreatic β‐cell dysfunction because of reduced β‐cell mass and function is a primary determinant in the progression of diabetes. Increase in β‐cell mass and compensatory hyperinsulinaemia is frequently associated with insulin‐resistant states. Although the humoral factors mediating this compensatory response are unknown, serpinB1, a protease inhibitor, has recently been proposed to be one such factor. In this study, we examine the relationships between plasma serpinB1, insulin sensitivity, and pancreatic β‐cell function in non‐diabetic individuals. 117 subjects (women, n = 50, men, n = 67; age= 37.6 ± 10.8; BMI=31.1 ± 7.7 kg/m2) underwent an insulin‐modified frequently sampled intravenous glucose tolerance test (FSIVGTT) at the NIH Clinical Research Center. Acute insulin response (AIR) and insulin sensitivity index (SI) were obtained from the FSIVGTT with MINMOD analysis. The Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated from fasting insulin and glucose values. Plasma serpinB1 levels were measured using an ELISA assay. Simple linear correlation analyses were performed to evaluate the relationship between serpinB1 and measures of insulin sensitivity and β‐cell function. Circulating serpinB1 levels were unrelated to age, sex, race, BMI, or percent body fat. SI but not AIR significantly correlated with circulating serpinB1 levels (r = 0.23, P < 0.05). QUICKI tended to positively correlate with serpinB1 (r = 0.16, P = 0.09). Circulating serpinB1 is directly associated with insulin sensitivity but not β‐cell function in non‐diabetic adults. Whether this modest association plays a role in insulin sensitivity in humans remains to be clarified.
Highlights
In insulin-resistant states, compensatory changes in b-cell mass and function are critical in maintaining normal plasma glucose homeostasis (Weir et al 2001)
Metabolites and peptides secreted by other organs, hormones derived from adipose tissue, as well as signals secreted by muscle and bone, have all been proposed as potential circulatory factors responsible for this phenomenon (Sachdeva and Stoffers 2009; El Ouaamari et al 2013; Dirice et al 2014)
In this study of healthy non-diabetic participants, serpinB1 was positively associated with insulin sensitivity derived from the frequently sampled intravenous glucose tolerance test (FSIVGTT) and unrelated to b-cell function
Summary
In insulin-resistant states, compensatory changes in b-cell mass and function are critical in maintaining normal plasma glucose homeostasis (Weir et al 2001). Liverspecific insulin receptor knockout in mice (LIRKO) upregulates pancreatic b-cell proliferation (El Ouaamari et al 2013; Dirice et al 2014). Using this model, El Ouaamari et al (2016), recently demonstrated serpinB1 as the hepatocyte-derived factor responsible for this b-cell proliferation. This article is a U.S Government work and is in the public domain in the USA.
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