23 - Pulsatile Administration of Insulin and Glucagon in Man

Abstract

Publisher Summary This chapter discusses the effects of pulsatile administration of insulin, glucagon, or both hormones together on carbohydrate metabolism and islet cell function. In one of the experiments, six healthy volunteers were submitted to a 325-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin. Glucagon was replaced at a continuous infusion rate of 67 ng/min, resulting in peripheral plasma glucagon levels similar to the preinfusion basal levels. No effect was observed on glucose utilization or metabolic clearance rate. In another experiment, pulsatile glucagon administration induced a greater stimulation of hepatic glucose output than an identical dose of the hormone infused continuously for 325 min. In the presence of somatostatin-induced insulin deficiency, with no insulin replacement, pulsatile glucagon induced greater rises in blood glucose, plasma nonesterified fatty acid, glycerol, and β-hydroxybutyrate levels than did its continuous delivery. When compared with pulsatile insulin and continuous glucagon, pulsatile glucagon and continuous insulin were characterized by significantly higher endogenous (hepatic) glucose production. When both insulin and glucagon were delivered in a pulsatile manner, the effect of pulsatile glucagon was predominant, maintaining a high endogenous glucose production.