Extrapancreatic effect of somatostatin infusion to increase glucose clearance

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Abstract
Constant intraportal insulin, coupled with variable intraportal glucagon, was used in the attempt to reestablish basal metabolic conditions in dogs during somatostatin (SRIF) infusion (0.8 micrograms X min-1 X kg-1). SRIF alone lowered glucose (G), insulin (I), and glucagon (GN) (G: 90 +/- 5 to 69 +/- 1 mg/dl; I: 18 +/- 4 to 4 +/- 1 microU/ml; GN: 257 +/- 52 to 168 +/- 40 pg/ml; P less than 0.05 or better). Hormone replacement. Hypoglycemia persisted (G at steady state, SS, 60–150 min): 12 +/- 3 mg/dl below basal; P = 0.006) despite intraportal insulin replacement (200 microU X min-1 X kg-1; insulin at basal: 14 +/- 1; at SS: 14 +/- 2 microU/ml; P greater than 0.9) and glucagon overreplacement (basal: 341 +/- 42; SS: 486 +/- 80 pg/ml; P less than 0.05). Glucose clearance was increased 65% above basal (P less than 0.0001). Insulin underreplacement. With a lower intraportal insulin infusion rate (50 microU X min-1 X kg-1), insulin fell from basal (10 +/- 2 microU/ml) to 4 +/- 1 microU/ml during steady state (P = 0.03). Glucose and glucose clearance were normalized to basal values (G: 85 +/- 3 mg/dl, P = 0.3; clearance: 5.7 +/- 0.5 ml X min-1 X kg-1; P = 0.2) with full glucagon replacement (basal: 281 +/- 120; SS: 264 +/- 80 pg/ml; P greater than 0.9). Thus, during constant SRIF infusion, normoglycemia was reattained when insulin was underreplaced via the portal vein. The failure to reattain euglycemia with normoinsulinemia was due to a SRIF-induced increase in extrahepatic glucose clearance. Insulin replacement and growth hormone (GH) infusion. GH (15 ng X min-1 X kg-1) partially reversed the hypoglycemia during SRIF, with full insulin replacement. The SRIF-induced increase in glucose clearance may be partially mediated by a decrease in GH.