Submitted on January 28, 2004
Accepted on March 25, 2004
Hepatic Glucose Autoregulation: Responses to Small Non-Insulin-Induced Changes in Arterial Glucose
Raul C. Camacho1*, D. Brooks Lacy1, Freyja D. James1, Robert H. Coker1, and David H. Wasserman1
1 Department of Molecular Physiology and Biophysics and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: Raul.Camacho{at}vanderbilt.edu.
Autoregulation of glucose production (Ra) is an important defense against overt
hypoglycemia during exercise. The purpose of this study was to determine whether the
body is able to autoregulate Ra in response to small non-insulin-induced changes (<20
mg.dL-1) in arterial plasma glucose. Dogs had sampling (artery, portal vein, hepatic vein)
and infusion (vena cava, portal vein, renal arteries) catheters, and flow probes (hepatic
artery, portal vein) implanted >16 days prior to a study. Protocols consisted of equilibration
(-130 to -30 min), basal (-30 to 0 min) and bilateral renal arterial phloridzin infusion (0 to
180 min) periods. SRIF was infused and glucagon and insulin were replaced in the portal
vein to maintain basal levels of pancreatic hormones. In one protocol (Phl±Glc), glucose
was allowed to fall from t=0 to 90 min. This was followed by a period where glucose was
infused to restore euglycemia (90 to 150 min), and a period where glucose was allowed to
fall again (150 to 180 min). In a second protocol (EC), glucose was infused to compensate
for the renal loss of glucose due to phloridzin, and maintain euglycemia using a clamp
technique from t=0 to 180 min. Arterial insulin, glucagon, cortisol, and catecholamines
were similar between groups and did not change during the study. In Phl±Glc, glucose fell
by ~20 mg.dL-1 by t=90 min, with phloridzin infusion. Glucose was returned to basal levels
with exogenous glucose infusion by t=105 min, and then fell again after t=150 min by ~20
mg.dL-1. Glucose was clamped at basal levels throughout the study in EC. Ra did not
change from basal with phloridzin infusion in Phl±Glc despite the fall in glucose for the first
90 min. Ra was significantly suppressed with a restoration of euglycemia from t=90 to 150
min (p<0.05), and returned to basal when glucose was allowed to fall again from t=150 to
180 min. Ra did not change from basal in EC with phloridzin and glucose infusion. In conclusion, as with exercise, the liver autoregulates Ra in response to small changes in
glucose independent of changes in pancreatic hormones at rest. However, in the resting dog
the liver is more sensitive to a small increment, rather than decrement, in arterial glucose.
