Hepatic glucose autoregulation: Responses to small, non-insulin-induced changes in arterial glucose

The purpose of this study was to determine whether the sedentary dog is able to autoregulate glucose production (R_a) in response to non-insulin-induced changes (<20 mg/dl) in arterial glucose. Dogs had catheters implanted >16 days before study. Protocols consisted of basal (-30 to 0 min) and bilateral renal arterial phloridzin infusion (0-180 min) periods. Somatostatin was infused, and glucagon and insulin were replaced to basal levels. In one protocol (Phl ± Glc), glucose was allowed to fall from t = 0-90 min. This was followed by a period when glucose was infused to restore euglycemia (90-150 min) and a period when glucose was allowed to fall again (150-180 min). In a second protocol (EC), glucose was infused to compensate for the renal glucose loss due to phloridzin and maintain euglycemia from t = 0-180 min. Arterial insulin, glucagon, cortisol, and catecholamines remained at basal in both protocols. In Phl ± Glc, glucose fell by ∼20 mg/dl by t = 90 min with phloridzin infusion. R_α did not change from basal in Phl ± Glc despite the fall in glucose for the first 90 min. R_a was significantly suppressed with restoration of euglycemia from t = 90-150 min (P < 0.05) and returned to basal when glucose was allowed to fall from t = 150-180 min. R_a did not change from basal in EC. In conclusion, the liver autoregulates R_a in response to small changes in glucose independently of changes in pancreatic hormones at rest. However, the liver of the resting dog is more sensitive to a small increment, rather than decrement, in arterial glucose.