Regulation of transforming growth factor-beta1 by insulin in prediabetic African Americans.
Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-beta1, a key cytokine associated with kidney disease, responds to circulating levels of glucose and/or insulin. Urinary TGF-beta1 levels were measured in 249 young adult African Americans (mean age 40) at baseline, after an oral glucose tolerance test and after a euglycemic hyperinsulinemic clamp procedure. Baseline urinary geometric mean TGF-beta1 levels were somewhat lower in those with normal compared with the impaired glucose tolerance. The urinary TGF-beta1 level increased by 56% followed by a 23% decrease in the normal glucose tolerance group, changes that were significant and corresponded to the changes in the plasma glucose and insulin concentrations. The impaired tolerance group showed little change in the urinary TGF-beta1 level following glucose ingestion. All participants had a significant increase in urinary TGF-beta1 level after steady-state hyperinsulinemia, with sustained euglycemia during the clamp procedure in both of the groups. At baseline, there was a significant correlation between the urinary TGF-beta1 level and urinary albumin excretion. Thus our results suggest that insulin contributes to increased TGF-beta1 production and possible early renal injury in prediabetic young African Americans.
Huan
Yonghong
Y
Division of Nephrology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
DeLoach
Stephanie
S
Daskalakis
Constantine
C
Dunn
Stephen R
SR
Sharma
Kumar
K
Falkner
Bonita
B
D000328:Adult; D001741:Black or African American; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D018149:Glucose Intolerance / Q000235:genetics; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007004:Hypoglycemic Agents / Q000097:blood*; D007328:Insulin / Q000097:blood*; D007674:Kidney Diseases / Q000652:urine; D008297:Male; D011236:Prediabetic State / Q000097:blood*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000097:blood / Q000652:urine
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D053773:Transforming Growth Factor beta1