Somatostatin Impairs Clearance of Exogenous Insulin in Humans

Somatostatin has been widely used to suppress endogenous pancreatic hormone secretion in research studies. Many of these studies required the simultaneous infusion of a hormone together with somatostatin. A critical assumption for its use in metabolic investigation is that somatostatin has no effect on the action or clearance of a concomitantly infused hormone. To test whether clearance of an exogenously infused hormone is affected, we infused insulin with or without somatostatin in two sets of studies. Insulin (40 mU · kg⁻¹ · h⁻¹) was infused for 100 min (n = 6). Plasma glucose levels fell to 55 ± 4.1 mg/dl with insulin alone and significantly lower, to 44 ± 1.9 mg/dl, when somatostatin (250 μg/h) was also infused (P < .01). Plasma immunoreactive insulin (IRI) rose to 57 ± 12.5 μU/ml with insulin alone, which was significantly different from 88 ± 15 μU/ml when insulin was infused together with somatostatin (P < .01). When a smaller dose of insulin (30 mU kg⁻¹ h⁻¹) was infused for 100 min (n = 4), similar results were observed. When somatostatin was infused together with insulin, plasma glucose fell to lower levels (41 ± 4.2 vs. 62 ± 9.5 mg/dl; P < .01) and plasma IRI rose higher (39 ± 8.5 vs. 27 ± 5.9 μU/ml; P < .01) than when insulin was infused alone. C-peptide was equally suppressed by hypoglycemia regardless of whether somatostatin was administered, indicating suppression of endogenous insulin during these studies. We conclude that somatostatin infusion impairs the clearance of exogenous insulin. The resulting higher plasma IRI levels may contribute to the exaggerated hypoglycemia observed when somatostatin is infused with insulin. Impairment of clearance must be considered in the interpretation of metabolic studies where insulin and perhaps other peptide hormones are infused together with somatostatin.