title: β-Cell Sensitivity to GLP-1 in Healthy Humans Is Variable and Proportional to Insulin Sensitivity.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance. Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degree to which people vary in their β-cell sensitivity to GLP-1 and the factors contributing to this variability have not been reported.
  
  
  OBJECTIVE
  The objective was to measure the sensitivity of insulin secretion to GLP-1 in cohorts of lean and obese subjects across a broad range of insulin sensitivity.
  
  
  METHODS
  Insulin secretion was measured during clamped hyperglycemia (7.2 mmol/L) and graded GLP-1 infusion in young, healthy subjects, and GLP-1 sensitivity was computed from the insulin secretion rate (ISR) during progressive increases in plasma GLP-1.
  
  
  RESULTS
  All subjects had fasting glucose values <5.2 mm. The obese subjects were insulin resistant compared to the lean group (homeostasis model of assessment 2 for insulin resistance: obese, 2.6 ± 0.5; lean, 0.8 ± 0.1; P < .001). ISR increased linearly in both cohorts with escalating doses of GLP-1, but the slope of ISR in response to GLP-1 was greater in the obese than in the lean subjects (obese, 0.17 ± 0.03 nmol/min/pm; lean, 0.05 ± 0.01 nmol/min/pm; P < .001). There was a significant association of β-cell GLP-1 sensitivity and insulin resistance (r = 0.83; P < .001), and after correction for homeostasis model of assessment 2 for insulin resistance, the slopes of ISR vs GLP-1 concentration did not differ in the two cohorts (obese, 0.08 ± 0.01; lean, 0.08 ± 0.01; P = .98). However, within the entire study group, β-cell GLP-1 sensitivity corrected for insulin resistance varied nearly 10-fold.
  
  
  CONCLUSIONS
  Insulin secretion in response to GLP-1 is proportional to insulin resistance in healthy subjects. However, there is considerable variability in the sensitivity of the β-cell to GLP-1 that is independent of insulin sensitivity.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
authors.forename: Benedikt A
authors.initials: BA
authors.lastname: Aulinger
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
authors.forename: Torsten P
authors.initials: TP
authors.lastname: Vahl
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
authors.forename: Hilary E
authors.initials: HE
authors.lastname: Wilson-Pérez
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
authors.forename: Ron L
authors.initials: RL
authors.lastname: Prigeon
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006262:Health; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism; D013851:Thinness / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1
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