263-OR: Counterregulatory Responses to Hypoglycemia in Totally Pancreatectomized Patients

We have previously shown that totally pancreatectomized (PX) patients secrete substantial amounts of glucagon (most likely from enteroendocrine cells) during an oral glucose tolerance test (OGTT) whereas these patients suppress circulating glucagon concentrations during intravenous glucose infusions. Here, we investigated the effect of insulin-induced hypoglycemia on extrapancreatic glucagon secretion and other counterregulatory factors in PX patients and in healthy controls (CTRLs). On two separate days, 12 PX patients (age 65.5±5.5 [mean±SD] years; BMI: 23.8±3.6 kg/m2) and 12 matched, healthy CTRLs (age 64.8±6.5 years; BMI: 24.5±2.9 kg/m2) underwent 1) a 50-g OGTT with 1.5 g acetaminophen (for assessment of gastric emptying) and 2) an insulin-induced hypoglycemic clamp followed by a 30-minute recovery period and a subsequent 50-g OGTT with acetaminophen. Blood was intermittently sampled throughout both experimental days. Plasma glucagon responses to OGTT (as assessed by baseline-subtracted area under curve) were greater in PX patients compared to CTRLs (386±150 vs. -340±50 min×pmol/l [mean±SEM], P=0.0001). During the hypoglycemic clamp, PX patients did not increase plasma glucagon concentrations and, thus, glucagon responses to hypoglycemia were higher in CTRLs (903±104 vs. -21±16 min×pmol/l, P Disclosure M. Baekdal: None. A.B. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. M. Baldassarre: None. J.I. Egholk: None. K. Rose: None. C. Hansen: None. J.H. Storkholm: None. M.B. Christensen: None. B. Hartmann: None. J. Faber: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. T. Vilsboll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S.