title: Plasma serpinB1 is related to insulin sensitivity but not pancreaticβ-Cell function in non-diabetic adults.
abstract: Pancreaticβ-cell dysfunction because of reducedβ-cell mass and function is a primary determinant in the progression of diabetes. Increase inβ-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 pancreaticβ-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 andβ-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 notβ-cell function in non-diabetic adults. Whether this modest association plays a role in insulin sensitivity in humans remains to be clarified.
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Glicksman
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland.
authors.forename: Asha
authors.initials: A
authors.lastname: Asthana
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Abel
authors.affiliation: Clinical Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Walter
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland.
authors.forename: Monica C
authors.initials: MC
authors.lastname: Skarulis
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland muniyapr@mail.nih.gov.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Muniyappa
mesh_terms: D000328:Adult; D001786:Blood Glucose; D003430:Cross-Sectional Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015843:Serpins / Q000097:blood*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015843:Serpins; C075177:SERPINB1 protein, human
keywords: Insulin resistance; Insulin sensitivity; SerpinB1; β‐cell function; β‐cell proliferation