Somatostatin infusion enhances hepatic glucose production during hyperglucagonemia

Abstract

Somatostatin (SRIH) is widely employed in metabolic studies to permit quantitation of glucose production and disposal rates while the endocrine pancreas is suppressed and the hormonal milieu is under the investigator's control. In these studies it is assumed that if peripheral levels of insulin and glucagon are the same during SRIH infusion as during control studies, the effects of these hormones on glucose metabolism are equivalent. If the effect of glucagon is influenced by SRIH infusion, then these techniques may be unsuitable for the study of the regulation of hepatic glucose output. To assess the influence of SRIH on glucagon-stimulated hepatic glucose production (Ra), we determined Ra during paired studies in ten healthy (five younger and five older) subjects. In each study an insulin infusion designed to yield physiologic systemic insulin levels of 20 to 30 μU/mL was given from 0 to 210 minutes. In addition, from 60 to 210 minutes either glucagon alone (3.5 ng/kg/min) (I + IRG) or glucagon (3.5 ng/kg/min) and SRIH (250 μgm/h) (I + IRG + SRIH) was infused. Since results for plasma levels of insulin, C-peptide, glucagon, and Ra were similar in young and old subjects, the two age groups were combined for analysis. Basal plasma insulin, glucagon, C-peptide, glucose, and Ra were similar in each arm of the study. Insulin values were nearly identical from 60 to 210 minutes (I + IRG, 23.8 ± 1.1; I + IRG + SRIH, 24.0 ± 1.0 μU/mL). During the insulin alone portion of the study (0 to 60 minutes), C-peptide levels fell to approximately 65% of basal (I + IRG, 64 ± 8%; I + IRG + SRIH, 69 ± 6%). From 60 to 210 minutes there was no significant further suppression of C-peptide during the I + IRG study, but during the I + IRG + SRIH study, C-peptide progressively declined to a value of 8 ± 1% of basal ( P < .01). The mean increment above basal in glucagon was slightly but not significantly greater during the I + IRG study (I + IRG, 409 ± 30; I + IRG + SRIH, 354 ± 33 pg/mL). Despite the lower glucagon levels during the I + IRG + SRIH infusion, the area under the curve for Ra from 60 to 210 minutes was greater in these studies (I + IRG, 2.13 ± 0.18; I + IRG + SRIH, 3.08 ± 0.20 mg/kg/min, P < .01). We conclude that SRIH augments glucagon-stimulated Ra in man. This effect is probably mediated through inhibition of endogenous insulin release.