Submitted on December 10, 2004
Accepted on February 9, 2005
Simulated First-Phase Insulin Release Using Humulin or an Insulin Analogue (HIM2) is Associated with Prolonged Improvement in Post-Prandial Glycemia
Catherine A. DiCostanzo1*, Mary Courtney Moore2, Margaret Lautz2, Melanie Scott2, Ben Farmer2, Carrie A. Everett2, J. Gordon Still2, Alan Higgins2, and Alan D. Cherrington2
1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Diabetes Research and Training Center, Vanderbilt University, Nashville, TN, USA
2 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: catherine.dicostanzo{at}vanderbilt.edu.
We examined the extent to which priming the liver with a pulse of humulin or an insulin analogue (HIM2) reduces postprandial hyperglycemia. Somatostatin (0.5 µg/kg/min) was given with basal intraportal insulin and glucagon for 4.5h into 3 groups of 42h fasted conscious dogs. From 0-5min, group one (BI, n=6) received saline, group two (HI, n=6) received a Humulin pulse (10 mU/kg/min), and group three (HIM2, n=6) received a
HIM2 pulse (10 mU/kg/min). Duodenal glucose was infused (5.0 mg/kg/min) from 15-270min. Arterial insulin (µU/ml) in BI remained basal (6±1), while it peaked at 52±15 (HI) and 164±44 (HIM2) and returned to baseline by 30 and 60 min, respectively. Arterial plasma glucose (mg/dl) plateaued at 265±20, 214±15 and 193±14 in BI, HI, and
HIM2. Glucose absorption was similar in all groups. Significant net hepatic glucose uptake occurred at 85, 55, and 25 min in BI, HI, and HIM2, respectively. Nonhepatic
glucose clearance (ml/kg/min) at 270min differed among groups (BI, HI, HIM2)0.62±0.11, 0.76±0.26, and 1.61±0.29 (P<0.05). A brief (5min) insulin pulse improved post-prandial glycemia, stimulating hepatic glucose uptake and prolonging enhancement of non-hepatic glucose clearance. HIM2 was more effective than Humulin perhaps because its lowered clearance caused higher levels at the liver and periphery and its biologic activity was not reduced proportionally to its decreased clearance.
