title: Arginine is preferred to glucagon for stimulation testing of β-cell function.
abstract: A key aspect of research into the prevention and treatment of type 2 diabetes is the availability of reproducible clinical research methodology to assess β-cell function. One commonly used method employs nonglycemic secretagogues like arginine (arg) or glucagon (glgn). This study was designed to quantify the insulin response to arg and glgn and determine test repeatability and tolerability. Obese overnight-fasted subjects with normal glucose tolerance were studied on 4 separate days: twice using arg (5 g iv) and twice with glgn (1 mg iv). Pre- and postinfusion samples for plasma glucose, insulin, and C-peptide were acquired. Arg and glgn challenges were repeated in the last 10 min of a 60-min glucose (900 mg/min) infusion. Insulin and C-peptide secretory responses were estimated under baseline fasting glucose conditions (AIRarg and AIRglgn) and hyperglycemic (AIRargMAX AIRglgnMAX) states. Relative repeatability was estimated by intraclass correlation coefficient (ICC). Twenty-three (12 men and 11 women) subjects were studied (age: 42.4 ± 8.3 yr; BMI: 31.4 ± 2.8 kg/m²). Geometric means (95% CI) for baseline-adjusted values AIRarg and AIRglgn were 84 (75-95) and 102 (90-115) μU/ml, respectively. After the glucose infusion, AIRargMAX and AIRglgnMAX were 395 (335-466) and 483 (355-658) μU/ml, respectively. ICC values were >0.90 for AIRarg andAIRargMAX. Glucagon ICCs were 0.83, 0.34, and 0.36, respectively, although the exclusion of one outlier increased the latter two values (to 0.84 and 0.86). Both glgn and arg induced mild adverse events that were transient. Glucagon, but not arginine, induced moderate adverse events due to nausea. Taken together, arginine is preferred to glucagon for assessment of β-cell function.
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, Washington;
authors.forename: R Paul
authors.initials: RP
authors.lastname: Robertson
authors.affiliation: R-Squared Solutions, Skillman, New Jersey;
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Raymond
authors.affiliation: Pfizer, Incorporated, Groton, Connecticut;
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Pfizer, Incorporated, Groton, Connecticut;
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Calle
authors.affiliation: Janssen Research and Development, Raritan, New Jersey;
authors.forename: Atalanta
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Savage
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana;
authors.forename: Sudha S
authors.initials: SS
authors.lastname: Shankar
authors.affiliation: Foundation for the National Institutes of Health, Bethesda, Maryland;
authors.forename: Maria T
authors.initials: MT
authors.lastname: Vassileva
authors.affiliation: Joslin Diabetes Center, Boston, Massachusetts; and.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: ROI BioPharma Consulting, East Lyme, Connecticut dfryburg@roibiopharma.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Fryburg
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000008:administration & dosage / Q000009:adverse effects; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009325:Nausea / Q000139:chemically induced; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology; D010292:Paresthesia / Q000139:chemically induced; D015203:Reproducibility of Results
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D001120:Arginine
keywords: arginine; glucagon; insulin secretion; β-cell function