GLUCOSE-TURNOVER AND RECYCLING IN DIABETES SECONDARY TO TOTAL PANCREATECTOMY - EFFECT OF GLUCAGON-INFUSION

This study was designed to evaluate whether chronic deficiency of pancreatic glucagon in patients with diabetes secondary to total pancreatectomy (PX) is responsible for the commonly observed increase in blood concentrations of gluconeogenic precursors (alanine, lactate, and pyruvate). Seven PX patients were studied on two different occasions: 1) after an overnight insulin infusion (0.15 mU/kgA min) and 2) after an overnight insulin/glucagon infusion (2 ng/kgA min). Five type 1 diabetic individuals were also studied after a similar overnight insulin infusion. In the morning of each study day, [6-3H]glucose and [1-14C]glucose were rapidly injected for determination of total glucose turnover rate ([6-3H]glucose) and glucose recycling (difference between [6-3H]glucose and [1-14C]glucose turnover rate). Basal concentrations of hormones, glucose, and intermediary metabolites were measured. After overnight insulin infusion, plasma glucose concentration (3.8 ± 0.4 vs. 6.8 ± 1.4 mmol/L), turnover rate (8.4 ± 1.0 vs. 13.7 ± 1.9 μmol/kgA min), and percent glucose recycling (5.6 ± 3.9% vs. 19.0 ± 3.8%) were significantly lower in PX patients than in type 1 diabetic individuals (P < 0.05–0.01). On the contrary, blood alanine (459 ± 93 vs. 263 ± 28 μmol/L), lactate (1157 ± 109 vs. 818 ± 116 μmol/L), and pyruvate (71 ± 8 vs. 42 ± 3 μmol/L) were significantly higher than those values in type 1 diabetic patients (P < 0.05–0.01). Insulin/glucagon infusion increased plasma glucose con centration (8.7 ± 1.5 mmol/L), total turnover (18.1 ± 1.7 μmol/ kgA min), and percent recycling (20.4 ± 6.6%) to values similar to those in type 1 diabetic subjects. The change in glucose metabolism was associated with a significant drop in blood concentrations of alanine (179 ± 24 μmol/L), lactate (611 ± μmol/L), and pyruvate (30 ± 3 μmol/L; all P < 0.05–0.01 vs. insulin infusion alone). In PX patients, the glucose turnover rate was inversely correlated with blood concentrations of both alanine (r = 0.67) and lactate (r = 0.71; P < 0.01). In conclusion, chronic deficiency of pancreatic glucagon in PX patients 1) associated with a decreased rate of glucose turnover, 2) causes marked impairment in glucose recycling (an index of the activity of hepatic gluconeogenesis), and 3) increases blood concentra tions of alanine, lactate, and pyruvate. All abnormalities reversed by glucagon. © 1990 by The Endocrine Society.