Contrasting Insulin Sensitivity of Endogenous Glucose Production Rate in Subjects With Hepatocyte Nuclear Factor-1β and -1α Mutations

• DOI: 10.2337/diabetes.55.02.06.db05-1019
• Publication Date: 2006-06-01T23:03:17Z
• Authors: Anna Brackenridge; Ewan R. Pearson; Fariba Shojaee-Mo...; Andrew T. Hattersley; David Russell-Jones; A. Margot Umpleby
• Keywords: Hyperinsulinemia; Hepatocyte nuclear factors

Heterozygous mutations in the transcription factors hepatocyte nuclear factor (HNF)-1α and -1β result MODY (maturity-onset diabetes of young). Despite structural similarity between HNF-1α -1β, HNF-1β mutation carriers have hyperinsulinemia, whereas normal or reduced insulin concentrations. We examined whether are resistant. The endogenous glucose production rate uptake were measured with a two-step, low-dose (0.3 mU · kg−1 min−1) high-dose (1.5 hyperinsulinemic-euglycemic clamp, an infusion [6,6-2H2]glucose, six subjects mutations, control subjects, matched for age, sex, BMI. Endogenous was not suppressed by but 89% (P = 0.004) 80% < 0.001). Insulin-stimulated suppression lipolysis similar all groups at low- insulin. Subjects sensitivity peripheral sensitivity. This is likely to reflect action liver possibly kidney. may be mediated through regulation key gluconeogenic enzymes glucose-6-phosphatase PEPCK.