Role of basal glucagon levels in the regulation of splanchnic glucose output and ketogenesis in insulin-deficient humans.
The aim of the present study was to investigate the influence of hepatic glycogen depletion and increased lipolysis on the response of splanchnic glucose output and ketogenesis to combined glucagon and insulin deficiency in normal man. Healthy subjects were studied after a 60-h fast and compared with a control group studied after an overnight fast. Net splanchnic exchange of glucose, gluconeogenic precursors, free fatty acids (FFA) and ketone acids were measured in the basal state and during intravenous infusion of somatostatin (9 micrograms/min) for 90-140 min (overnight fasted subjects) or for 5 h (60-h fasted subjects). During the infusion of somatostatin, euglycemia was maintained by a variable intravenous infusion of glucose. Prior to somatostatin infusion, after an overnight (12-14 h) fast, splanchnic uptake of glucose precursors (alanine, lactate, pyruvate, glycerol) could account for 26% of splanchnic glucose output (SGO) indicating primarily glycogenolysis. Somatostatin infusion resulted in a 50% reduction in both insulin and glucagon concentrations and a transient decline in SGO which returned to baseline values by 86 +/- 11 min at which point the glucose infusion was no longer necessary to maintain euglycemia. Arterial concentrations of FFA and beta-OH-butyrate and splanchnic beta-OH-butyrate production rose 2.5-fold, 6-fold and 7.5-fold, respectively, in response to somatostatin infusion. In the 60-h fasted state, basal SGO (0.29 +/- 0.03 mmol/min) was 60% lower than after an overnight fast and basal splanchnic uptake of glucose precursors could account for 85% of SGO, indicating primarily gluconeogenesis. Somatostatin administration suppressed the arterial glucagon and insulin concentrations to values comparable to those observed during the infusion in the overnight fasted state. SGO fell promptly in response to the somatostatin infusion and in contrast to the overnight fasted state, remained inhibited by 50-100% for 5 h. Infusion of glucose was consequently necessary to maintain euglycemia throughout the 5-h infusion of somatostatin. Splanchnic uptake of gluconeogenic precursors was unchanged during somatostatin despite the sustained suppression of SGO. Basal arterial concentration and splanchnic exchange of beta-OH-butyrate were respectively 22-fold and 6- to 7-fold elevated and basal FFA concentration was 70% increased as compared to the corresponding values in the overnight fasted state.(ABSTRACT TRUNCATED AT 400 WORDS)
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000172:deficiency*; D007659:Ketones / Q000096:biosynthesis*; D008297:Male; D013004:Somatostatin / Q000494:pharmacology; D013152:Splanchnic Circulation; D013997:Time Factors
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007659:Ketones; D013004:Somatostatin; D005934:Glucagon